The school of nature III. From mechanistic understanding to novel therapies

Self/Nonself - Immune Recognition and Signaling

Volumn 1, Issue 3, 2010, Pages 192-224

  Sigalov, Alexander B ^a  

^a SignaBlok Inc   (United States)

Author keywords

Arthritis; Cancer; Cell activation; Cytoplasmic homointeractions; Dermatitis; Human cytomegalovirus; Human immunodeficiency virus; Immune disorders; Immune response; Immunomodulators; Inflammatory bowel diseases; Inflammatory conditions; Intrinsically disordered proteins; Mechanistic model; Membrane receptors; MIRR; Multichain immune recognition receptors; Novel therapies; Peptide inhibitors; Peptides; Peptidomimetics; Platelet disorders; Platelet inhibition; Protein protein interactions; Receptor inhibitors; SCHOOL model; Sepsis; Severe acute respiratory syndrome coronavirus; Signaling chain homooligomerization model; Single chain receptors; Small molecules; Stent thrombosis; Therapeutic targets; Thrombosis; Transmembrane interactions; Transmembrane signal transduction; Viral pathogenesis

Indexed keywords

ANTICOAGULANT AGENT; BETA ADRENERGIC RECEPTOR; CD3 ANTIGEN; COLLAGEN; CONVULXIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERYTHROPOIETIN RECEPTOR; FAS ANTIGEN; FC RECEPTOR; G PROTEIN COUPLED RECEPTOR; GLYCOPROTEIN GP 41; GLYCOPROTEIN IIB; GLYCOPROTEIN VI; GRANULOCYTE COLONY STIMULATING FACTOR RECEPTOR; IMMUNOGLOBULIN E; MEMBRANE RECEPTOR; MYELOID DIFFERENTIATION FACTOR 88; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 3; NATURAL KILLER CELL RECEPTOR NKG2D; NEF PROTEIN; NEUTRALIZING ANTIBODY; PEPTIDE FRAGMENT; PROTEIN TYROSINE KINASE; SYNTHETIC PEPTIDE; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN; TRANSFORMING GROWTH FACTOR BETA; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 1; UNINDEXED DRUG;

ALLERGIC DISEASE; ALLERGY; ATOPIC DERMATITIS; BLEEDING; COLITIS; CYTOPLASM; DRUG TARGETING; ENTERITIS; HEMORRHAGIC SHOCK; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMAN T CELL LEUKEMIA VIRUS INFECTION; NEOPLASM; NONHUMAN; OLIGOMERIZATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; RECEPTOR BINDING; RECEPTOR INTRINSIC ACTIVITY; REVIEW; RHEUMATOID ARTHRITIS; SEPSIS; SEPTIC SHOCK; SEVERE ACUTE RESPIRATORY SYNDROME; SIGNAL TRANSDUCTION; SIGNALING CHAIN HOMOOLIGOMERIZATION MODEL; THROMBOSIS; VIRUS PATHOGENESIS;

EID: 78049318071     PISSN: 19382030     EISSN: 19382049     Source Type: Journal    
DOI: 10.4161/self.1.3.12794     Document Type: Review

References (336)

1. Fry DC. Protein-protein interactions as targets for small molecule drug discovery. Biopolymers 2006; 84:535-52.
2. Ryan DP, Matthews JM. Protein-protein interactions in human disease. Curr Opin Struct Biol 2005; 15:441-6.
3. Toogood PL. Inhibition of protein-protein association by small molecules: approaches and progress. J Med Chem 2002; 45:1543-58.
4. Fletcher S, Hamilton AD. Targeting protein-protein interactions by rational design: mimicry of protein surfaces. J R Soc Interface 2006; 3:215-33.
5. Hershberger SJ, Lee SG, Chmielewski J. Scaffolds for blocking protein-protein interactions. Curr Top Med Chem 2007; 7:928-42.
6. Loregian A, Palu G. Disruption of protein-protein interactions: towards new targets for chemotherapy. J Cell Physiol 2005; 204:750-62.
7. Sillerud LO, Larson RS. Design and structure of peptide and peptidomimetic antagonists of protein-protein interaction. Curr Protein Pept Sci 2005; 6:151-69.
8. Che Y, Brooks BR, Marshall GR. Development of small molecules designed to modulate protein-protein interactions. J Comput Aided Mol Des 2006; 20:109-30.
9. Berg T. Modulation of protein-protein interactions with small organic molecules. Angew Chem Int Ed Engl 2003; 42:2462-81.
10. Archakov AI, Govorun VM, Dubanov AV, Ivanov YD, Veselovsky AV, Lewi P, et al. Protein-protein interactions as a target for drugs in proteomics. Proteomics 2003; 3:380-91.
11. Veselovsky AV, Ivanov YD, Ivanov AS, Archakov AI, Lewi P, Janssen P. Protein-protein interactions: mechanisms and modification by drugs. J Mol Recognit 2002; 15:405-22.
12. Pagliaro L, Felding J, Audouze K, Nielsen SJ, Terry RB, Krog-Jensen C, et al. Emerging classes of protein-protein interaction inhibitors and new tools for their development. Curr Opin Chem Biol 2004; 8:442-9.
13. Sugaya N, Ikeda K. Assessing the druggability of protein-protein interactions by a supervised machine-learning method. BMC Bioinformatics 2009; 10:263.
14. Veselovsky AV, Archakov AI. Inhibitors of protein-protein interactions as potential drugs. Curr Comput Aided Drug Des 2007; 3:51-8.
15. Zhong S, Macias AT, MacKerell AD Jr. Computational identification of inhibitors of protein-protein interactions. Curr Top Med Chem 2007; 7:63-82.
16. Fry DC. Drug-like inhibitors of protein-protein interactions: a structural examination of effective protein mimicry. Curr Protein Pept Sci 2008; 9:240-7.
17. Fry DC, Vassilev LT. Targeting protein-protein interactions for cancer therapy. J Mol Med 2005; 83:955-63.
18. Berg T. Small-molecule inhibitors of protein-protein interactions. Curr Opin Drug Discov Devel 2008; 11:666-74.
19. Fletcher S, Hamilton AD. Protein-protein interaction inhibitors: small molecules from screening techniques. Curr Top Med Chem 2007; 7:922-7.
20. Robinson JA. Design of protein-protein interaction inhibitors based on protein epitope mimetics. Chembiochem 2009; 10:971-3.
21. Casey FP, Pihan E, Shields DC. Discovery of small molecule inhibitors of protein-protein interactions using combined ligand and target score normalization. J Chem Inf Model 2009; 49:2708-17.
22. Yang RY, Yang KS, Pike LJ, Marshall GR. Targeting the dimerization of epidermal growth factor receptors with small-molecule inhibitors. Chem Biol Drug Des 2010; 76:1-9.
23. Stockwell BR. Exploring biology with small organic molecules. Nature 2004; 432:846-54.
24. Arkin M. Protein-protein interactions and cancer: small molecules going in for the kill. Curr Opin Chem Biol 2005; 9:317-24.
25. Bose M, Gestwicki JE, Devasthali V, Crabtree GR, Graef IA. 'Nature-inspired' drug-protein complexes as inhibitors of Abeta aggregation. Biochem Soc Trans 2005; 33:543-7.
26. Watt PM. Screening for peptide drugs from the natural repertoire of biodiverse protein folds. Nat Biotechnol 2006; 24:177-83.
27. Stoevesandt O, Elbs M, Kohler K, Lellouch AC, Fischer R, Andre T, et al. Peptide microarrays for the detection of molecular interactions in cellular signal transduction. Proteomics 2005; 5:2010-7.
28. Rudd CE. Disabled receptor signaling and new primary immunodeficiency disorders. N Engl J Med 2006; 354:1874-7.
29. Sigalov AB, ed. Multichain immune recognition receptor signaling: From spatiotemporal organization to human disease. New York: Springer-Verlag 2008.
30. Sigalov AB. Multichain immune recognition receptor signaling: different players, same game? Trends Immunol 2004; 25:583-9.
31. Sigalov AB. Immune cell signaling: a novel mechanistic model reveals new therapeutic targets. Trends Pharmacol Sci 2006; 27:518-24.
32. Sigalov AB. SCHOOL model and new targeting strategies. Adv Exp Med Biol 2008; 640:268-311.
33. Sigalov AB. Signaling chain homooligomerization (SCHOOL) model. Adv Exp Med Biol 2008; 640:121-63.
34. Sigalov AB. The SCHOOL of nature. I. Transmembrane signaling. Self/Nonself-Immune Recognition and Signaling 2010; 1:4-39.
35. Sigalov AB. Protein intrinsic disorder and oligomericity in cell signaling. Mol Biosyst 2010; 6:451-61.
36. Norman PS. Immunotherapy: 1999-2004. J Allergy Clin Immunol 2004; 113:1013-23.
37. Jackson SP, Schoenwaelder SM. Antiplatelet therapy: in search of the 'magic bullet'. Nat Rev Drug Discov 2003; 2:775-89.
38. Kepley CL. New approaches to allergen immunotherapy. Curr Allergy Asthma Rep 2006; 6:427-33.
39. Kraft S, Kinet JP. New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 2007; 7:365-78.
40. McNicol A, Israels SJ. Platelets and anti-platelet therapy. J Pharmacol Sci 2003; 93:381-96.
41. Molloy PE, Sewell AK, Jakobsen BK. Soluble T cell receptors: novel immunotherapies. Curr Opin Pharmacol 2005; 5:438-43.
42. Pons L, Burks W. Novel treatments for food allergy. Expert Opin Investig Drugs 2005; 14:829-34.
43. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 2007; 7:622-32.
44. St. Clair EW, Turka LA, Saxon A, Matthews JB, Sayegh MH, Eisenbarth GS, et al. New reagents on the horizon for immune tolerance. Annu Rev Med 2007; 58:329-46.
45. Hombach A, Heuser C, Abken H. The recombinant T cell receptor strategy: insights into structure and function of recombinant immunoreceptors on the way towards an optimal receptor design for cellular immunotherapy. Curr Gene Ther 2002; 2:211-26.
46. Luzak B, Golanski J, Rozalski M, Bonclerand MA, Watala C. Inhibition of collagen-induced platelet reactivity by DGEA peptide. Acta Biochim Pol 2003; 50:1119-28.
47. O'Herrin SM, Slansky JE, Tang Q, Markiewicz MA, Gajewski TF, Pardoll DM, et al. Antigen-specific blockade of T cells in vivo using dimeric MHC peptide. J Immunol 2001; 167:2555-60.
48. Andrasfalvy M, Peterfy H, Toth G, Matko J, Abramson J, Kerekes K, et al. The beta subunit of the type I Fcepsilon receptor is a target for peptides inhibiting IgE-mediated secretory response of mast cells. J Immunol 2005; 175:2801-6.
49. Cronin SJ, Penninger JM. From T-cell activation signals to signaling control of anti-cancer immunity. Immunol Rev 2007; 220:151-68.
50. Waldmann TA. Immune receptors: targets for therapy of leukemia/lymphoma, autoimmune diseases and for the prevention of allograft rejection. Annu Rev Immunol 1992; 10:675-704.
51. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010; 9:325-38.
52. Sigalov A, Aivazian D, Stern L. Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain and of other proteins containing the immunoreceptor tyrosine-based activation motif. Biochemistry 2004; 43:2049-61.
53. Sigalov AB, Zhuravleva AV, Orekhov VY. Binding of intrinsically disordered proteins is not necessarily accompanied by a structural transition to a folded form. Biochimie 2007; 89:419-21.
54. Sigalov A. Multi-chain immune recognition receptors: spatial organization and signal transduction. Semin Immunol 2005; 17:51-64.
55. Sigalov AB. The SCHOOL of nature. II. Protein order, disorder and oligomericity in transmembrane signaling. Self/Nonself-Immune Recognition and Signaling 2010; 1:89-102.
56. Finger C, Escher C, Schneider D. The single transmembrane domains of human receptor tyrosine kinases encode self-interactions. Sci Signal 2009; 2:56.
57. Li E, Hristova K. Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. Biochemistry 2006; 45:6241-51.
58. Smith SO, Smith C, Shekar S, Peersen O, Ziliox M, Aimoto S. Transmembrane interactions in the activation of the Neu receptor tyrosine kinase. Biochemistry 2002; 41:9321-32.
59. Li E, Hristova K. Receptor tyrosine kinase transmembrane domains: Function, dimer structure and dimerization energetics. Cell Adh Migr 2010; 4:249-54.
60. Tanner KG, Kyte J. Dimerization of the extracellular domain of the receptor for epidermal growth factor containing the membrane-spanning segment in response to treatment with epidermal growth factor. J Biol Chem 1999; 274:35985-90.
61. Fantl WJ, Johnson DE, Williams LT. Signalling by receptor tyrosine kinases. Annu Rev Biochem 1993; 62:453-81.
62. Heldin CH. Dimerization of cell surface receptors in signal transduction. Cell 1995; 80:213-23.
63. Hubbard SR. Structural analysis of receptor tyrosine kinases. Prog Biophys Mol Biol 1999; 71:343-58.
64. Weiss A, Schlessinger J. Switching signals on or off by receptor dimerization. Cell 1998; 94:277-80.
65. Schlessinger J. Signal transduction. Autoinhibition control. Science 2003; 300:750-2.
66. Cooper JA, Qian H. A mechanism for SRC kinase-dependent signaling by noncatalytic receptors. Biochemistry 2008; 47:5681-8.
67. Klemm JD, Schreiber SL, Crabtree GR. Dimerization as a regulatory mechanism in signal transduction. Annu Rev Immunol 1998; 16:569-92.
68. Jiang G, Hunter T. Receptor signaling: when dimerization is not enough. Curr Biol 1999; 9:568-71.
69. Marianayagam NJ, Sunde M, Matthews JM. The power of two: protein dimerization in biology. Trends Biochem Sci 2004; 29:618-25.
70. Siegel RM, Muppidi JR, Sarker M, Lobito A, Jen M, Martin D, et al. SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane. J Cell Biol 2004; 167:735-44.
71. Chan FK. Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 2007; 37:101-7.
72. Chan KF, Siegel MR, Lenardo JM. Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 2000; 13:419-22.
73. Keegan AD, Paul WE. Multichain immune recognition receptors: similarities in structure and signaling pathways. Immunol Today 1992; 13:63-8.
74. Reth M. Antigen receptor tail clue. Nature 1989; 338:383-4.
75. Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, et al. SH2 domains recognize specific phosphopeptide sequences. Cell 1993; 72:767-78.
76. Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med 2000; 192:1059-68.
77. Manolios N, Bonifacino JS, Klausner RD. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science 1990; 249:274-7.
78. Call ME, Pyrdol J, Wiedmann M, Wucherpfennig KW. The organizing principle in the formation of the T cell receptor-CD3 complex. Cell 2002; 111:967-79.
79. Michnoff CH, Parikh VS, Lelsz DL, Tucker PW. Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig alpha and Igbeta association and signal transduction. J Biol Chem 1994; 269:24237-44.
80. Daeron M. Fc receptor biology. Annu Rev Immunol 1997; 15:203-34.
81. Borrego F, Kabat J, Kim DK, Lieto L, Maasho K, Pena J, et al. Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol Immunol 2002; 38:637-60.
82. Biassoni R, Cantoni C, Falco M, Pende D, Millo R, Moretta L, et al. Human natural killer cell activating receptors. Mol Immunol 2000; 37:1015-24.
83. Moroi M, Jung SM. Platelet glycoprotein VI: its structure and function. Thromb Res 2004; 114:221-33.
84. Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266-73.
85. Feng J, Garrity D, Call ME, Moffett H, Wucherpfennig KW. Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors. Immunity 2005; 22:427-38.
86. Feng J, Call ME, Wucherpfennig KW. The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site. PLoS Biol 2006; 4:142.
87. Bakema JE, de Haij S, den Hartog-Jager CF, Bakker J, Vidarsson G, van Egmond M, et al. Signaling through mutants of the IgA receptor CD89 and consequences for Fc receptor gamma-chain interaction. J Immunol 2006; 176:3603-10.
88. Varin-Blank N, Metzger H. Surface expression of mutated subunits of the high affinity mast cell receptor for IgE. J Biol Chem 1990; 265:15685-94.
89. Stevens TL, Blum JH, Foy SP, Matsuuchi L, DeFranco AL. A mutation of the mu transmembrane that disrupts endoplasmic reticulum retention. Effects on association with accessory proteins and signal transduction. J Immunol 1994; 152:4397-406.
90. Zidovetzki R, Rost B, Pecht I. Role of transmembrane domains in the functions of B- and T-cell receptors. Immunol Lett 1998; 64:97-107.
91. Blum JH, Stevens TL, DeFranco AL. Role of the mu immunoglobulin heavy chain transmembrane and cytoplasmic domains in B cell antigen receptor expression and signal transduction. J Biol Chem 1993; 268:27236-45.
92. Barclay AN, Brown MH. The SIRP family of receptors and immune regulation. Nat Rev Immunol 2006; 6:457-64.
93. Fujimoto M, Takatsu H, Ohno H. CMRF-35-like molecule-5 constitutes novel paired receptors, with CMRF-35-like molecule-1, to transduce activation signal upon association with FcRgamma. Int Immunol 2006; 18:1499-508.
94. Ra C, Jouvin MH, Kinet JP. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem 1989; 264:15323-7.
95. Boniface JJ, Rabinowitz JD, Wulfing C, Hampl J, Reich Z, Altman JD, et al. Initiation of signal transduction through the T cell receptor requires the multivalent engagement of peptide/MHC ligands [corrected]. Immunity 1998; 9:459-66.
96. Holowka D, Baird B. Antigen-mediated IGE receptor aggregation and signaling: a window on cell surface structure and dynamics. Annu Rev Biophys Biomol Struct 1996; 25:79-112.
97. Thyagarajan R, Arunkumar N, Song W. Polyvalent antigens stabilize B cell antigen receptor surface signaling microdomains. J Immunol 2003; 170:6099-106.
98. Bankovich AJ, Raunser S, Juo ZS, Walz T, Davis MM, Garcia KC. Structural insight into pre-B cell receptor function. Science 2007; 316:291-4.
99. Puffer EB, Pontrello JK, Hollenbeck JJ, Kink JA, Kiessling LL. Activating B cell signaling with defined multivalent ligands. ACS Chem Biol 2007; 2:252-62.
100. Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, et al. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat Immunol 2007; 8:398-408.
101. Adams EJ, Chien YH, Garcia KC. Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22. Science 2005; 308:227-31.
102. Bachmann MF, Ohashi PS. The role of T-cell receptor dimerization in T-cell activation. Immunol Today 1999; 20:568-76.
103. Bachmann MF, Salzmann M, Oxenius A, Ohashi PS. Formation of TCR dimers/trimers as a crucial step for T cell activation. Eur J Immunol 1998; 28:2571-9.
104. DeFranco AL, Gold MR, Jakway JP. B-lymphocyte signal transduction in response to anti-immunoglobulin and bacterial lipopolysaccharide. Immunol Rev 1987; 95:161-76.
105. Posner RG, Savage PB, Peters AS, Macias A, DelGado J, Zwartz G, et al. A quantitative approach for studying IgE-FcepsilonRI aggregation. Mol Immunol 2002; 38:1221-8.
106. Draberova L, Lebduska P, Halova I, Tolar P, Stokrova J, Tolarova H, et al. Signaling assemblies formed in mast cells activated via Fcepsilon receptor I dimers. Eur J Immunol 2004; 34:2209-19.
107. Horii K, Kahn ML, Herr AB. Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI. Blood 2006; 108:936-42.
108. Cochran JR, Cameron TO, Stern LJ. The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers. Immunity 2000; 12:241-50.
109. Fahmy TM, Bieler JG, Schneck JP. Probing T cell membrane organization using dimeric MHC-Ig complexes. J Immunol Methods 2002; 268:93-106.
110. Kiessling LL, Gestwicki JE, Strong LE. Synthetic multivalent ligands as probes of signal transduction. Angew Chem Int Ed Engl 2006; 45:2348-68.
111. Garrity D, Call ME, Feng J, Wucherpfennig KW. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Proc Natl Acad Sci USA 2005; 102:7641-6.
112. Radaev S, Kattah M, Rostro B, Colonna M, Sun PD. Crystal structure of the human myeloid cell activating receptor TREM-1. Structure 2003; 11:1527-35.
113. Ortega E. How do multichain immune recognition receptors signal? A structural hypothesis. Mol Immunol 1995; 32:941-5.
114. Berlanga O, Bori-Sanz T, James JR, Frampton J, Davis SJ, Tomlinson MG, et al. Glycoprotein VI oligomerization in cell lines and platelets. J Thromb Haemost 2007; 5:1026-33.
115. Symer DE, Dintzis RZ, Diamond DJ, Dintzis HM. Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays. J Exp Med 1992; 176:1421-30.
116. Schweitzer-Stenner R, Tamir I, Pecht I. Analysis of Fc(epsilon)RI-mediated mast cell stimulation by surface-carried antigens. Biophys J 1997; 72:2470-8.
117. Patrick SM, Kim S, Braunstein NS, Thomas JL, Leonard EF. Dependence of T cell activation on area of contact and density of a ligand-coated surface. J Immunol Methods 2000; 241:97-108.
118. Germain RN. T-cell signaling: the importance of receptor clustering. Curr Biol 1997; 7:640-4.
119. Alam SM, Davies GM, Lin CM, Zal T, Nasholds W, Jameson SC, et al. Qualitative and quantitative differences in T cell receptor binding of agonist and antagonist ligands. Immunity 1999; 10:227-37.
120. Lemmon MA, Schlessinger J. Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 1994; 19:459-63.
121. Minguet S, Dopfer EP, Schamel WW. Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor (BCR). Int Immunol 2010; 22:205-12.
122. Harwood NE, Batista FD. Early events in B cell activation. Annu Rev Immunol 2010; 28:185-210.
123. Herr AB. Direct evidence of a native GPVI dimer at the platelet surface. J Thromb Haemost 2009; 7:1344-6.
124. Horii K, Brooks MT, Herr AB. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: implications for platelet activation. Biochemistry 2009; 48:2907-14.
125. Jung SM, Tsuji K, Moroi M. Glycoprotein (GP) VI dimer as a major collagen-binding site of native platelets: direct evidence obtained with dimeric GPVI-specific Fabs. J Thromb Haemost 2009; 7:1347-55.
126. Varma R. TCR triggering by the pMHC complex: valency, affinity and dynamics. Sci Signal 2008; 1:21.
127. Schamel WW, Arechaga I, Risueno RM, van Santen HM, Cabezas P, Risco C, et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J Exp Med 2005; 202:493-503.
128. Strong RK. Asymmetric ligand recognition by the activating natural killer cell receptor NKG2D, a symmetric homodimer. Mol Immunol 2002; 38:1029-37.
129. Li P, Morris DL, Willcox BE, Steinle A, Spies T, Strong RK. Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat Immunol 2001; 2:443-51.
130. Steinle A, Li P, Morris DL, Groh V, Lanier LL, Strong RK, et al. Interactions of human NKG2D with its ligands MICA, MICB and homologs of the mouse RAE-1 protein family. Immunogenetics 2001; 53:279-87.
131. Sigalov AB, Aivazian DA, Uversky VN, Stern LJ. Lipid-binding activity of intrinsically unstructured cytoplasmic domains of multichain immune recognition receptor signaling subunits. Biochemistry 2006; 45:15731-9.
132. Sigalov AB. New therapeutic strategies targeting transmembrane signal transduction in the immune system. Cell Adh Migr 2010; 4:255-67.
133. Sigalov AB. Transmembrane interactions as immunotherapeutic targets: lessons from viral pathogenesis. Adv Exp Med Biol 2007; 601:335-44.
134. Sigalov AB. Novel mechanistic concept of platelet inhibition. Expert Opin Ther Targets 2008; 12:677-92.
135. McDonnell JM, Beavil AJ, Mackay GA, Jameson BA, Korngold R, Gould HJ, et al. Structure based design and characterization of peptides that inhibit IgE binding to its high-affinity receptor. Nat Struct Biol 1996; 3:419-26.
136. Stevenson CL. Advances in peptide pharmaceuticals. Curr Pharm Biotechnol 2009; 10:122-37.
137. Sigalov AB. Interaction between HIV gp41 fusion peptide and T cell receptor: putting the puzzle pieces back together. Faseb J 2007; 21:1633-4.
138. Sigalov AB. More on: glycoprotein VI oligomerization: a novel concept of platelet inhibition. J Thromb Haemost 2007; 5:2310-2.
139. Kim WM, Sigalov AB. Viral pathogenesis, modulation of immune receptor signaling and treatment. Adv Exp Med Biol 2008; 640:325-49.
140. Sigalov AB. Novel mechanistic insights into viral modulation of immune receptor signaling. PLoS Pathog 2009; 5:1000404.
141. Sigalov AB. Multichain immune recognition receptor signaling from spatiotemporal organization to human disease. Preface. Adv Exp Med Biol 2008; 640:ix-xi.
142. Metzger H. Transmembrane signaling: the joy of aggregation. J Immunol 1992; 149:1477-87.
143. Mass RD. The HER receptor family: a rich target for therapeutic development. Int J Radiat Oncol Biol Phys 2004; 58:932-40.
144. Daniel PT, Wieder T, Sturm I, Schulze-Osthoff K. The kiss of death: promises and failures of death receptors and ligands in cancer therapy. Leukemia 2001; 15:1022-32.
145. Hernanz-Falcon P, Rodriguez-Frade JM, Serrano A, Juan D, del Sol A, Soriano SF, et al. Identification of amino acid residues crucial for chemokine receptor dimerization. Nat Immunol 2004; 5:216-23.
146. Holler N, Tardivel A, Kovacsovics-Bankowski M, Hertig S, Gaide O, Martinon F, et al. Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death-inducing signaling complex. Mol Cell Biol 2003; 23:1428-40.
147. Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys 2004; 58:903-13.
148. Mendrola JM, Berger MB, King MC, Lemmon MA. The single transmembrane domains of ErbB receptors self-associate in cell membranes. J Biol Chem 2002; 277:4704-12.
149. Vandenabeele P, Declercq W, Beyaert R, Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol 1995; 5:392-9.
150. Wang J, Norcross M. Dimerization of chemokine receptors in living cells: key to receptor function and novel targets for therapy. Drug Discov Today 2008; 13:625-32.
151. Bennasroune A, Fickova M, Gardin A, Dirrig-Grosch S, Aunis D, Cremel G, et al. Transmembrane peptides as inhibitors of ErbB receptor signaling. Mol Biol Cell 2004; 15:3464-74.
152. Cymer F, Schneider D. Transmembrane helix-helix interactions involved in ErbB receptor signaling. Cell Adh Migr 2010; 4:299-312.
153. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, et al. A peptide derived from a beta2- adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 1996; 271:16384-92.
154. George SR, Lee SP, Varghese G, Zeman PR, Seeman P, Ng GY, et al. A transmembrane domain-derived peptide inhibits D1 dopamine receptor function without affecting receptor oligomerization. J Biol Chem 1998; 273:30244-8.
155. Yin H, Litvinov RI, Vilaire G, Zhu H, Li W, Caputo GA, et al. Activation of platelet alphaIIbbeta3 by an exogenous peptide corresponding to the transmembrane domain of alphaIIb. J Biol Chem 2006; 281:36732-41.
156. Tarasova NI, Rice WG, Michejda CJ. Inhibition of G-protein-coupled receptor function by disruption of transmembrane domain interactions. J Biol Chem 1999; 274:34911-5.
157. Bennasroune A, Gardin A, Auzan C, Clauser E, Dirrig- Grosch S, Meira M, et al. Inhibition by transmembrane peptides of chimeric insulin receptors. Cell Mol Life Sci 2005; 62:2124-31.
158. Bennett JS. Structure and function of the platelet integrin alphaIIbbeta3. J Clin Invest 2005; 115:3363-9.
159. Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 2006; 125:1137-49.
160. Syed RS, Reid SW, Li C, Cheetham JC, Aoki KH, Liu B, et al. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature 1998; 395:511-6.
161. Livnah O, Johnson DL, Stura EA, Farrell FX, Barbone FP, You Y, et al. An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation. Nat Struct Biol 1998; 5:993-1004.
162. Ballinger MD, Wells JA. Will any dimer do? Nat Struct Biol 1998; 5:938-40.
163. Gay NJ, Gangloff M, Weber AN. Toll-like receptors as molecular switches. Nat Rev Immunol 2006; 6:693-8.
164. Neiditch MB, Federle MJ, Pompeani AJ, Kelly RC, Swem DL, Jeffrey PD, et al. Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing. Cell 2006; 126:1095-108.
165. Dosch DD, Ballmer-Hofer K. Transmembrane domain-mediated orientation of receptor monomers in active VEGFR-2 dimers. Faseb J 2010; 24:32-8.
166. Lofts FJ, Hurst HC, Sternberg MJ, Gullick WJ. Specific short transmembrane sequences can inhibit transformation by the mutant neu growth factor receptor in vitro and in vivo. Oncogene 1993; 8:2813-20.
167. Martin K, Meade G, Moran N, Shields DC, Kenny D. A palmitylated peptide derived from the glycoprotein Ib beta cytoplasmic tail inhibits platelet activation. J Thromb Haemost 2003; 1:2643-52.
168. Chaudhry A, Das SR, Jameel S, George A, Bal V, Mayor S, et al. A two-pronged mechanism for HIV-1 Nef-mediated endocytosis of immune costimulatory molecules CD80 and CD86. Cell Host Microbe 2007; 1:37-49.
169. Stephens G, O'Luanaigh N, Reilly D, Harriott P, Walker B, Fitzgerald D, et al. A sequence within the cytoplasmic tail of GpIIb independently activates platelet aggregation and thromboxane synthesis. J Biol Chem 1998; 273:20317-22.
170. Liu J, Jackson CW, Gruppo RA, Jennings LK, Gartner TK. The beta3 subunit of the integrin alphaIIbbeta3 regulates alphaIIb-mediated outside-in signaling. Blood 2005; 105:4345-52.
171. Loiarro M, Capolunghi F, Fanto N, Gallo G, Campo S, Arseni B, et al. Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc Biol 2007; 82:801-10.
172. Loiarro M, Sette C, Gallo G, Ciacci A, Fanto N, Mastroianni D, et al. Peptide-mediated interference of TIR domain dimerization in MyD88 inhibits interleukin-1-dependent activation of NF-{kappa}B. J Biol Chem 2005; 280:15809-14.
173. Hartlieb B, Modrof J, Muhlberger E, Klenk HD, Becker S. Oligomerization of Ebola virus VP30 is essential for viral transcription and can be inhibited by a synthetic peptide. J Biol Chem 2003; 278:41830-6.
174. Clark AJ, Petty HR. A cell permeant peptide containing the cytoplasmic tail sequence of Fc receptor type IIA reduces calcium signaling and phagolysosome formation in neutrophils. Cell Immunol 2010; 261:153-8.
175. Thorburn A. Death receptor-induced cell killing. Cell Signal 2004; 16:139-44.
176. Wajant H. The Fas signaling pathway: more than a paradigm. Science 2002; 296:1635-6.
177. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4:499-511.
178. O'Neill LA. The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochem Soc Trans 2003; 31:643-7.
179. Liu LX, Heveker N, Fackler OT, Arold S, Le Gall S, Janvier K, et al. Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions. J Virol 2000; 74:5310-9.
180. Berndt MC, Shen Y, Dopheide SM, Gardiner EE, Andrews RK. The vascular biology of the glycoprotein Ib-IX-V complex. Thromb Haemost 2001; 86:178-88.
181. Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84:289-97.
182. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995; 332:1553-9.
183. Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood 1998; 91:2645-57.
184. Coppolino M, Leung-Hagesteijn C, Dedhar S, Wilkins J. Inducible interaction of integrin alpha2beta1 with calreticulin. Dependence on the activation state of the integrin. J Biol Chem 1995; 270:23132-8.
185. Hughes PE, Diaz-Gonzalez F, Leong L, Wu C, McDonald JA, Shattil SJ, et al. Breaking the integrin hinge. A defined structural constraint regulates integrin signaling. J Biol Chem 1996; 271:6571-4.
186. Weitzman JB, Pujades C, Hemler ME. Integrin alpha chain cytoplasmic tails regulate "antibody-redirected" cell adhesion, independently of ligand binding. Eur J Immunol 1997; 27:78-84.
187. Gonzalez JP, Pourrut X, Leroy E. Ebolavirus and other filoviruses. Curr Top Microbiol Immunol 2007; 315:363-87.
188. Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol 1999; 73:2333-42.
189. Visintin A, Latz E, Monks BG, Espevik T, Golenbock DT. Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction. J Biol Chem 2003; 278:48313-20.
190. Zhang H, Tay PN, Cao W, Li W, Lu J. Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling. FEBS Lett 2002; 532:171-6.
191. Michnick SW, Remy I, Campbell-Valois FX, Vallee- Belisle A, Pelletier JN. Detection of protein-protein interactions by protein fragment complementation strategies. Methods Enzymol 2000; 328:208-30.
192. Lee HK, Dunzendorfer S, Tobias PS. Cytoplasmic domain-mediated dimerizations of toll-like receptor 4 observed by beta-lactamase enzyme fragment complementation. J Biol Chem 2004; 279:10564-74.
193. Pietersz GA, Mottram PL, van de Velde NC, Sardjono CT, Esparon S, Ramsland PA, et al. Inhibition of destructive autoimmune arthritis in FcgammaRIIa transgenic mice by small chemical entities. Immunol Cell Biol 2009; 87:3-12.
194. Tan Sardjono C, Mottram PL, Hogarth PM. The role of FcgammaRIIa as an inflammatory mediator in rheumatoid arthritis and systemic lupus erythematosus. Immunol Cell Biol 2003; 81:374-81.
195. Powell MS, Barnes NC, Bradford TM, Musgrave IF, Wines BD, Cambier JC, et al. Alteration of the Fc gamma RIIa dimer interface affects receptor signaling but not ligand binding. J Immunol 2006; 176:7489-94.
196. Enk AH, Knop J. T cell receptor mimic peptides and their potential application in T-cell-mediated disease. Int Arch Allergy Immunol 2000; 123:275-81.
197. Wang XM, Djordjevic JT, Kurosaka N, Schibeci S, Lee L, Williamson P, et al. T-cell antigen receptor peptides inhibit signal transduction within the membrane bilayer. Clin Immunol 2002; 105:199-207.
198. Collier S, Bolte A, Manolios N. Discrepancy in CD3- transmembrane peptide activity between in vitro and in vivo T-cell inhibition. Scand J Immunol 2006; 64:388-91.
199. Manolios N, Ali M, Amon M, Bender V. Therapeutic application of transmembrane T and natural killer cell receptor peptides. Adv Exp Med Biol 2008; 640:208-19.
200. Manolios N, Ali M, Bender V. T-cell antigen receptor (TCR) transmembrane peptides: A new paradigm for the treatment of autoimmune diseases. Cell Adh Migr 2010; 4:273-83.
201. Manolios N, Huynh NT, Collier S. Peptides in the treatment of inflammatory skin disease. Australas J Dermatol 2002; 43:226-7.
202. Amon MA, Ali M, Bender V, Chan YN, Toth I, Manolios N. Lipidation and glycosylation of a T cell antigen receptor (TCR) transmembrane hydrophobic peptide dramatically enhances in vitro and in vivo function. Biochim Biophys Acta 2006; 1763:879-88.
203. Amon MA, Ali M, Bender V, Hall K, Aguilar MI, Aldrich-Wright J, et al. Kinetic and conformational properties of a novel T-cell antigen receptor transmembrane peptide in model membranes. J Pept Sci 2008; 14:714-24.
204. Manolios N, Collier S, Taylor J, Pollard J, Harrison LC, Bender V. T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease. Nat Med 1997; 3:84-8.
205. Quintana FJ, Gerber D, Kent SC, Cohen IR, Shai Y. HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation. J Clin Invest 2005; 115:2149-58.
206. Bloch I, Quintana FJ, Gerber D, Cohen T, Cohen IR, Shai Y. T-Cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif. Faseb J 2007; 21:393-401.
207. Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci USA 1996; 93:13-20.
208. Ali M, Salam NK, Amon M, Bender V, Hibbs DE, Manolios N. T-Cell Antigen Receptor-alpha Chain Transmembrane Peptides: Correlation between Structure and Function. Int J Pept Res Ther 2006; 12:261-7.
209. Melnyk RA, Partridge AW, Yip J, Wu Y, Goto NK, Deber CM. Polar residue tagging of transmembrane peptides. Biopolymers 2003; 71:675-85.
210. Cunningham F, Deber CM. Optimizing synthesis and expression of transmembrane peptides and proteins. Methods 2007; 41:370-80.
211. Yin H, Slusky JS, Berger BW, Walters RS, Vilaire G, Litvinov RI, et al. Computational design of peptides that target transmembrane helices. Science 2007; 315:1817-22.
212. Wimley WC, White SH. Designing transmembrane alpha-helices that insert spontaneously. Biochemistry 2000; 39:4432-42.
213. Edwards RJ, Moran N, Devocelle M, Kiernan A, Meade G, Signac W, et al. Bioinformatic discovery of novel bioactive peptides. Nat Chem Biol 2007; 3:108-12.
214. Apic G, Russell RB. A shortcut to peptides to modulate platelets. Nat Chem Biol 2007; 3:83-4.
215. Ashish, Wimley WC. Visual detection of specific, native interactions between soluble and microbead-tethered alpha-helices from membrane proteins. Biochemistry 2001; 40:13753-9.
216. Killian JA. Synthetic peptides as models for intrinsic membrane proteins. FEBS Lett 2003; 555:134-8.
217. Vandebona H, Ali M, Amon M, Bender V, Manolios N. Immunoreceptor transmembrane peptides and their effect on natural killer (NK) cell cytotoxicity. Protein Pept Lett 2006; 13:1017-24.
218. Gollner GP, Muller G, Alt R, Knop J, Enk AH. Therapeutic application of T cell receptor mimic peptides or cDNA in the treatment of T cell-mediated skin diseases. Gene Ther 2000; 7:1000-4.
219. Kurosaka N, Bolte A, Ali M, Manolios N. T-cell antigen receptor assembly and cell surface expression is not affected by treatment with T-cell antigen receptor-alpha chain transmembrane Peptide. Protein Pept Lett 2007; 14:299-303.
220. Ali M, De Planque MRR, Huynh NT, Manolios N, Separovic F. Biophysical studies of a transmembrane peptide derived from the T cell antigen receptor. Lett Pept Sci 2002; 8:227-33.
221. Huynh NT, Ffrench RA, Boadle RA, Manolios N. Transmembrane T-cell receptor peptides inhibit B-and natural killer-cell function. Immunology 2003; 108:458-64.
222. Bender V, Ali M, Amon M, Diefenbach E, Manolios N. T cell antigen receptor peptide-lipid membrane interactions using surface plasmon resonance. J Biol Chem 2004; 279:54002-7.
223. Gerber D, Quintana FJ, Bloch I, Cohen IR, Shai Y. D-enantiomer peptide of the TCRalpha transmembrane domain inhibits T-cell activation in vitro and in vivo. Faseb J 2005; 19:1190-2.
224. Ali M, Amon M, Bender V, Manolios N. Hydrophobic transmembrane-peptide lipid conjugations enhance membrane binding and functional activity in T-cells. Bioconjug Chem 2005; 16:1556-63.
225. Wang XM, Djordjevic JT, Bender V, Manolios N. T cell antigen receptor (TCR) transmembrane peptides colocalize with TCR, not lipid rafts, in surface membranes. Cell Immunol 2002; 215:12-9.
226. Luton F, Buferne M, Legendre V, Chauvet E, Boyer C, Schmitt-Verhulst AM. Role of CD3gamma and CD3delta cytoplasmic domains in cytolytic T lymphocyte functions and TCR/CD3 down-modulation. J Immunol 1997; 158:4162-70.
227. Roifman CM. CD3delta immunodeficiency. Curr Opin Allergy Clin Immunol 2004; 4:479-84.
228. Shani N, Rubin-Lifshitz H, Peretz-Cohen Y, Shkolnik K, Shinder V, Cohen-Sfady M, et al. Incomplete T-cell receptor-beta peptides target the mitochondrion and induce apoptosis. Blood 2009; 113:3530-41.
229. Haks MC, Pepin E, van den Brakel JH, Smeele SA, Belkowski SM, Kessels HW, et al. Contributions of the T cell receptor-associated CD3gamma-ITAM to thymocyte selection. J Exp Med 2002; 196:1-13.
230. Haks MC, Cordaro TA, van den Brakel JH, Haanen JB, de Vries EF, Borst J, et al. A redundant role of the CD3 gamma-immunoreceptor tyrosine-based activation motif in mature T cell function. J Immunol 2001; 166:2576-88.
231. Torres PS, Alcover A, Zapata DA, Arnaud J, Pacheco A, Martin-Fernandez JM, et al. TCR dynamics in human mature T lymphocytes lacking CD3gamma. J Immunol 2003; 170:5947-55.
232. Sigalov AB. Inhibiting Collagen-induced Platelet Aggregation and Activation with Peptide Variants. US 12/001,258 and PCT PCT/US2007/025389 patent applications filed on 12/11/2007 and 12/12/2007, respectively, claiming a priority to US 60/874,694 provisional patent application filed on 12/13/2006.
233. Dyson HJ, Wright PE. Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 2005; 6:197-208.
234. Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradovic Z. Intrinsic disorder and protein function. Biochemistry 2002; 41:6573-82.
235. Iakoucheva LM, Brown CJ, Lawson JD, Obradovic Z, Dunker AK. Intrinsic disorder in cell-signaling and cancer-associated proteins. J Mol Biol 2002; 323:573-84.
236. Minezaki Y, Homma K, Nishikawa K. Intrinsically disordered regions of human plasma membrane proteins preferentially occur in the cytoplasmic segment. J Mol Biol 2007; 368:902-13.
237. Iakoucheva LM, Radivojac P, Brown CJ, O'Connor TR, Sikes JG, Obradovic Z, et al. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res 2004; 32:1037-49.
238. Sigalov AB, Kim WM, Saline M, Stern LJ. The intrinsically disordered cytoplasmic domain of the T cell receptor zeta chain binds to the Nef protein of simian immunodeficiency virus without a disorder-to-order transition. Biochemistry 2008; 47:12942-4.
239. Tompa P, Fuxreiter M. Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem Sci 2008; 33:2-8.
240. Mittag T, Kay LE, Forman-Kay JD. Protein dynamics and conformational disorder in molecular recognition. J Mol Recognit 2010; 23:105-16.
241. Dyson HJ, Wright PE. Equilibrium NMR studies of unfolded and partially folded proteins. Nat Struct Biol 1998; 5:499-503.
242. Dyson HJ, Wright PE. Unfolded proteins and protein folding studied by NMR. Chem Rev 2004; 104:3607-22.
243. Durell SR, Martin I, Ruysschaert JM, Shai Y, Blumenthal R. What studies of fusion peptides tell us about viral envelope glycoprotein-mediated membrane fusion (review). Mol Membr Biol 1997; 14:97-112.
244. Pecheur EI, Sainte-Marie J, Bienven eA, Hoekstra D. Peptides and membrane fusion: towards an understanding of the molecular mechanism of protein-induced fusion. J Membr Biol 1999; 167:1-17.
245. Weissenhorn W, Hinz A, Gaudin Y. Virus membrane fusion. FEBS Lett 2007; 581:2150-5.
246. Epand RM. Fusion peptides and the mechanism of viral fusion. Biochim Biophys Acta 2003; 1614:116-21.
247. Eckert DM, Kim PS. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 2001; 70:777-810.
248. Teissier E, Pecheur EI. Lipids as modulators of membrane fusion mediated by viral fusion proteins. Eur Biophys J 2007; 36:887-99.
249. Fackler OT, Alcover A, Schwartz O. Modulation of the immunological synapse: a key to HIV-1 pathogenesis? Nat Rev Immunol 2007; 7:310-7.
250. Stevenson M. HIV-1 pathogenesis. Nat Med 2003; 9:853-60.
251. Bosch ML, Earl PL, Fargnoli K, Picciafuoco S, Giombini F, Wong-Staal F, et al. Identification of the fusion peptide of primate immunodeficiency viruses. Science 1989; 244:694-7.
252. Gallaher WR. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus. Cell 1987; 50:327-8.
253. van Praag RM, Prins JM, Roos MT, Schellekens PT, Ten Berge IJ, Yong SL, et al. OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion. J Clin Immunol 2001; 21:218-26.
254. Blumenthal R, Dimitrov DS. Targeting the Sticky Fingers of HIV-1. Cell 2007; 129:243-5.
255. Munch J, Standker L, Adermann K, Schulz A, Schindler M, Chinnadurai R, et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell 2007; 129:263-75.
256. Bell I, Ashman C, Maughan J, Hooker E, Cook F, Reinhart TA. Association of simian immunodeficiency virus Nef with the T-cell receptor (TCR)zeta chain leads to TCR down-modulation. J Gen Virol 1998; 79:2717-27.
257. Schaefer TM, Bell I, Fallert BA, Reinhart TA. The T-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus Nef interacts and mediates down-modulation. J Virol 2000; 74:3273-83.
258. Schaefer TM, Bell I, Pfeifer ME, Ghosh M, Trible RP, Fuller CL, et al. The conserved process of TCR/CD3 complex down-modulation by SIV Nef is mediated by the central core, not endocytic motifs. Virology 2002; 302:106-22.
259. Keppler OT, Tibroni N, Venzke S, Rauch S, Fackler OT. Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1. J Leukoc Biol 2006; 79:616-27.
260. Schrager JA, Marsh JW. HIV-1 Nef increases T cell activation in a stimulus-dependent manner. Proc Natl Acad Sci USA 1999; 96:8167-72.
261. Simmons A, Aluvihare V, McMichael A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity 2001; 14:763-77.
262. Djordjevic JT, Schibeci SD, Stewart GJ, Williamson P. HIV type 1 Nef increases the association of T cell receptor (TCR)-signaling molecules with T cell rafts and promotes activation-induced raft fusion. AIDS Res Hum Retroviruses 2004; 20:547-55.
263. Krautkramer E, Giese SI, Gasteier JE, Muranyi W, Fackler OT. Human immunodeficiency virus type 1 Nef activates p21-activated kinase via recruitment into lipid rafts. J Virol 2004; 78:4085-97.
264. Xu XN, Laffert B, Screaton GR, Kraft M, Wolf D, Kolanus W, et al. Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. J Exp Med 1999; 189:1489-96.
265. Swigut T, Greenberg M, Skowronski J. Cooperative interactions of simian immunodeficiency virus Nef, AP-2 and CD3-zeta mediate the selective induction of T-cell receptor-CD3 endocytosis. J Virol 2003; 77:8116-26.
266. Arold S, Hoh F, Domergue S, Birck C, Delsuc MA, Jullien M, et al. Characterization and molecular basis of the oligomeric structure of HIV-1 nef protein. Protein Sci 2000; 9:1137-48.
267. Chen J, Subbarao K. The immunobiology of SARS*. Annu Rev Immunol 2007; 25:443-72.
268. Cui W, Fan Y, Wu W, Zhang F, Wang JY, Ni AP. Expression of lymphocytes and lymphocyte subsets in patients with severe acute respiratory syndrome. Clin Infect Dis 2003; 37:857-9.
269. Douek D. HIV disease progression: immune activation, microbes and a leaky gut. Top HIV Med 2007; 15:114-7.
270. Hazenberg MD, Hamann D, Schuitemaker H, Miedema F. T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat Immunol 2000; 1:285-9.
271. Gallaher WR, Ball JM, Garry RF, Griffin MC, Montelaro RC. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses 1989; 5:431-40.
272. Gallaher WR. Similar structural models of the transmembrane proteins of Ebola and avian sarcoma viruses. Cell 1996; 85:477-8.
273. Xu Y, Lou Z, Liu Y, Pang H, Tien P, Gao GF, et al. Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. J Biol Chem 2004; 279:49414-9.
274. Zhu J, Xiao G, Xu Y, Yuan F, Zheng C, Liu Y, et al. Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors. Biochem Biophys Res Commun 2004; 319:283-8.
275. Ingallinella P, Bianchi E, Finotto M, Cantoni G, Eckert DM, Supekar VM, et al. Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus. Proc Natl Acad Sci USA 2004; 101:8709-14.
276. Taguchi F, Shimazaki YK. Functional analysis of an epitope in the S2 subunit of the murine coronavirus spike protein: involvement in fusion activity. J Gen Virol 2000; 81:2867-71.
277. Bosch BJ, Martina BE, Van Der Zee R, Lepault J, Haijema BJ, Versluis C, et al. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA 2004; 101:8455-60.
278. Sainz B Jr, Rausch JM, Gallaher WR, Garry RF, Wimley WC. Identification and characterization of the putative fusion peptide of the severe acute respiratory syndrome-associated coronavirus spike protein. J Virol 2005; 79:7195-206.
279. Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 2007; 7:266-81.
280. Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, et al. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA 1981; 78:6476-80.
281. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA 1980; 77:7415-9.
282. Jones KS, Fugo K, Petrow-Sadowski C, Huang Y, Bertolette DC, Lisinski I, et al. Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor complexes to enter T cells. J Virol 2006; 80:8291-302.
283. Fukumoto R, Dundr M, Nicot C, Adams A, Valeri VW, Samelson LE, et al. Inhibition of T-cell receptor signal transduction and viral expression by the linker for activation of T cells-interacting p12(I) protein of human T-cell leukemia/lymphoma virus type 1. J Virol 2007; 81:9088-99.
284. Tsukahara T, Ratner L. Substitution of HIV Type 1 Nef with HTLV-1 p12. AIDS Res Hum Retroviruses 2004; 20:938-43.
285. Lin HC, Hickey M, Hsu L, Medina D, Rabson AB. Activation of human T cell leukemia virus type 1 LTR promoter and cellular promoter elements by T cell receptor signaling and HTLV-1 Tax expression. Virology 2005; 339:1-11.
286. Wilson KA, Bar S, Maerz AL, Alizon M, Poumbourios P. The conserved glycine-rich segment linking the N-terminal fusion peptide to the coiled coil of human T-cell leukemia virus type 1 transmembrane glycoprotein gp21 is a determinant of membrane fusion function. J Virol 2005; 79:4533-9.
287. Wilson KA, Maerz AL, Poumbourios P. Evidence that the transmembrane domain proximal region of the human T-cell leukemia virus type 1 fusion glycoprotein gp21 has distinct roles in the prefusion and fusion-activated states. J Biol Chem 2001; 276:49466-75.
288. Albrecht B, D'Souza CD, Ding W, Tridandapani S, Coggeshall KM, Lairmore MD. Activation of nuclear factor of activated T cells by human T-lymphotropic virus type 1 accessory protein p12(I). J Virol 2002; 76:3493-501.
289. Ding W, Albrecht B, Kelley RE, Muthusamy N, Kim SJ, Altschuld RA, et al. Human T-cell lymphotropic virus type 1 p12(I) expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells. J Virol 2002; 76:10374-82.
290. Nicot C, Mulloy JC, Ferrari MG, Johnson JM, Fu K, Fukumoto R, et al. HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells. Blood 2001; 98:823-9.
291. Albrecht B, Collins ND, Burniston MT, Nisbet JW, Ratner L, Green PL, et al. Human T-lymphotropic virus type 1 open reading frame I p12(I) is required for efficient viral infectivity in primary lymphocytes. J Virol 2000; 74:9828-35.
292. Collins ND, Newbound GC, Albrecht B, Beard JL, Ratner L, Lairmore MD. Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo. Blood 1998; 91:4701-7.
293. Fenard D, Yonemoto W, de Noronha C, Cavrois M, Williams SA, Greene WC. Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement. J Immunol 2005; 175:6050-7.
294. Guma M, Angulo A, Lopez-Botet M. NK cell receptors involved in the response to human cytomegalovirus infection. Curr Top Microbiol Immunol 2006; 298:207-23.
295. Arnon TI, Achdout H, Levi O, Markel G, Saleh N, Katz G, et al. Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Nat Immunol 2005; 6:515-23.
296. Biassoni R. Natural killer cell receptors. Adv Exp Med Biol 2008; 640:35-52.
297. Klewitz C, Klenk HD, ter Meulen J. Amino acids from both N-terminal hydrophobic regions of the Lassa virus envelope glycoprotein GP-2 are critical for pH-dependent membrane fusion and infectivity. J Gen Virol 2007; 88:2320-8.
298. Weiss HJ. Platelet physiology and abnormalities of platelet function (first of two parts). N Engl J Med 1975; 293:531-41.
299. Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, et al. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20:2120-30.
300. Leslie M. Cell biology. Beyond clotting: the powers of platelets. Science 2010; 328:562-4.
301. Angiolillo DJ, Bhatt DL, Gurbel PA, Jennings LK. Advances in antiplatelet therapy: agents in clinical development. Am J Cardiol 2009; 103:40-51.
302. Clemetson KJ. Platelet receptors and their role in diseases. Clin Chem Lab Med 2003; 41:253-60.
303. Michelson AD. Platelet inhibitor therapy: mechanisms of action and clinical use. J Thromb Thrombolysis 2003; 16:13-5.
304. Smethurst PA, Onley DJ, Jarvis GE, O'Connor MN, Knight CG, Herr AB, et al. Structural basis for the platelet-collagen interaction: the smallest motif within collagen that recognizes and activates platelet Glycoprotein VI contains two glycine-proline-hydroxyproline triplets. J Biol Chem 2007; 282:1296-304.
305. Gibbins JM, Okuma M, Farndale R, Barnes M, Watson SP. Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Lett 1997; 413:255-9.
306. Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood 2003; 102:449-61.
307. Jung SM, Moroi M. Platelet glycoprotein VI. Adv Exp Med Biol 2008; 640:53-63.
308. Li H, Lockyer S, Concepcion A, Gong X, Takizawa H, Guertin M, et al. The Fab fragment of a novel anti- GPVI monoclonal antibody, OM4, reduces in vivo thrombosis without bleeding risk in rats. Arterioscler Thromb Vasc Biol 2007; 27:1199-205.
309. Lockyer S, Okuyama K, Begum S, Le S, Sun B, Watanabe T, et al. GPVI-deficient mice lack collagen responses and are protected against experimentally induced pulmonary thromboembolism. Thromb Res 2006; 118:371-80.
310. Clemetson KJ. Platelet collagen receptors: a new target for inhibition? Haemostasis 1999; 29:16-26.
311. Massberg S, Konrad I, Bultmann A, Schulz C, Munch G, Peluso M, et al. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. Faseb J 2004; 18:397-9.
312. Muzard J, Bouabdelli M, Zahid M, Ollivier V, Lacapere JJ, Jandrot-Perrus M, et al. Design and humanization of a murine scFv that blocks human platelet glycoprotein VI in vitro. Febs J 2009; 276:4207-22.
313. Farndale RW. Collagen-induced platelet activation. Blood Cells Mol Dis 2006; 36:162-5.
314. Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium. Cardiovasc Res 2004; 61:498-511.
315. Collins B, Hollidge C. Antithrombotic drug market. Nat Rev Drug Discov 2003; 2:11-2.
316. Novak N. New insights into the mechanism and management of allergic diseases: atopic dermatitis. Allergy 2009; 64:265-75.
317. Akdis CA, Akdis M, Trautmann A, Blaser K. Immune regulation in atopic dermatitis. Curr Opin Immunol 2000; 12:641-6.
318. Kurosaka N, Ali M, Byth K, Manolios N. The mode of anti-arthritic peptide delivery impacts on the severity and outcome of adjuvant induced arthritis. APLAR J Rheumatol 2007; 10:198-203.
319. Kukar M, Petryna O, Efthimiou P. Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs. Biologics 2009; 3:443-57.
320. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001; 410:1103-7.
321. Ford JW, McVicar DW. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol 2009; 21:38-46.
322. Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 2000; 164:4991-5.
323. Gibot S, Massin F, Alauzet C, Derive M, Montemont C, Collin S, et al. Effects of the TREM 1 pathway modulation during hemorrhagic shock in rats. Shock 2009; 32:633-7.
324. Murakami Y, Akahoshi T, Aoki N, Toyomoto M, Miyasaka N, Kohsaka H. Intervention of an inflammation amplifier, triggering receptor expressed on myeloid cells 1, for treatment of autoimmune arthritis. Arthritis Rheum 2009; 60:1615-23.
325. Ho CC, Liao WY, Wang CY, Lu YH, Huang HY, Chen HY, et al. TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer. Am J Respir Crit Care Med 2008; 177:763-70.
326. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28:573-621.
327. Neurath MF, Finotto S. Translating inflammatory bowel disease research into clinical medicine. Immunity 2009; 31:357-61.
328. Allez M, Tieng V, Nakazawa A, Treton X, Pacault V, Dulphy N, et al. CD4+NKG2D+ T cells in Crohn's disease mediate inflammatory and cytotoxic responses through MICA interactions. Gastroenterology 2007; 132:2346-58.
329. Ito Y, Kanai T, Totsuka T, Okamoto R, Tsuchiya K, Nemoto Y, et al. Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis. Am J Physiol Gastrointest Liver Physiol 2008; 294:199-207.
330. Kjellev S, Haase C, Lundsgaard D, Urso B, Tornehave D, Markholst H. Inhibition of NKG2D receptor function by antibody therapy attenuates transfer-induced colitis in SCID mice. Eur J Immunol 2007; 37:1397-406.
331. Gianfrani C, Auricchio S, Troncone R. Adaptive and innate immune responses in celiac disease. Immunol Lett 2005; 99:141-5.
332. Ogasawara K, Hamerman JA, Ehrlich LR, Bour-Jordan H, Santamaria P, Bluestone JA, et al. NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity 2004; 20:757-67.
333. Vilarinho S, Ogasawara K, Nishimura S, Lanier LL, Baron JL. Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus. Proc Natl Acad Sci USA 2007; 104:18187-92.
334. Kim J, Chang CK, Hayden T, Liu FC, Benjamin J, Hamerman JA, et al. The activating immunoreceptor NKG2D and its ligands are involved in allograft transplant rejection. J Immunol 2007; 179:6416-20.
335. Suarez-Alvarez B, Lopez-Vazquez A, Baltar JM, Ortega F, Lopez-Larrea C. Potential role of NKG2D and its ligands in organ transplantation: new target for immunointervention. Am J Transplant 2009; 9:251-7.
336. Kraft S, Novak N. Fc receptors as determinants of allergic reactions. Trends Immunol 2006; 27:88-95.