Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

Current Topics in Medicinal Chemistry

Volumn 11, Issue 24, 2011, Pages 2985-2996

  Huarte, Nerea ^a   Lorizate, Maier ^b   Pérez Payá, Enrique ^c,d   Nieva, José L ^a  

^a UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE   (Spain)

^d INSTITUTO DE BIOMEDICINA DE VALENCIA   (Spain)

Author keywords

Anti MPER antibody; HIV 1 fusion inhibition; HIV 1 fusion peptide; HIV 1 gp41; HIV 1 MPER

Indexed keywords

ANTIVIRUS AGENT; DODECYLPHOSPHORYLCHOLINE; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS 1 FUSION PROTEIN; MEMBRANE PROTEIN; MEMBRANE PROXIMAL EXTERNAL REGION PROTEIN; PEPTIDE DERIVATIVE; PHOSPHOLIPID; UNCLASSIFIED DRUG; VIR 165; VIR 576; VIRUS FUSION PROTEIN; VIRUS INHIBITORY PEPTIDE;

AMINO ACID SEQUENCE; ANTIVIRAL ACTIVITY; ARTICLE; CELL FUSION; COMBINATORIAL CHEMISTRY; COMBINATORIAL LIBRARY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG TARGETING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; IN VITRO STUDY; LIPID COMPOSITION; NONHUMAN; PROTEIN FUNCTION; PROTEIN ISOLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; VIRUS ENVELOPE; VIRUS NEUTRALIZATION;

ANTIBODIES, NEUTRALIZING; CELL MEMBRANE; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV-1; HUMANS; PEPTIDES; VIRUS INTERNALIZATION;

EID: 84855243161     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/156802611798808460     Document Type: Article

References (122)

1. Blumenthal, R.; Clague, M. J.; Durell, S. R.; Epand, R. M. Membrane fusion. Chem. Rev., 2003, 103(1), 53-69.
2. Chernomordik, L. V.; Kozlov, M. M. Protein-lipid interplay in fusion and fission of biological membranes. Annu. Rev. Biochem., 2003, 72, 175-207.
3. Lentz, B. R.; Malinin, V.; Haque, M. E.; Evans, K. Protein machines and lipid assemblies: current views of cell membrane fusion. Curr. Opin. Struct. Biol., 2000, 10(5), 607-615.
4. Zimmerberg, J.; Vogel, S. S.; Chernomordik, L. V. Mechanisms of membrane fusion. Annu. Rev. Biophys. Biomol. Struct., 1993, 22, 433-466.
5. Doms, R. W.; Moore, J. P. HIV-1 membrane fusion: targets of opportunity. J. Cell Biol., 2000, 151(2), F9-14.
6. Eckert, D. M.; Kim, P. S. Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem., 2001, 70, 777-810.
7. Gallo, S. A.; Finnegan, C. M.; Viard, M.; Raviv, Y.; Dimitrov, A.; Rawat, S. S.; Puri, A.; Durell, S.; Blumenthal, R. The HIV Env-mediated fusion reaction. Biochim. Biophys. Acta, 2003, 1614(1), 36-50.
8. Wyatt, R.; Sodroski, J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science, 1998, 280(5371), 1884-1888.
9. Schibli, D. J.; Weissenhorn, W. Class I and class II viral fusion protein structures reveal similar principles in membrane fusion. Mol. Membr. Biol., 2004, 21(6), 361-371.
10. Weissenhorn, W.; Hinz, A.; Gaudin, Y. Virus membrane fusion. FEBS Lett., 2007, 581(11), 2150-2155.
11. Skehel, J. J.; Wiley, D. C. Receptor binding and membrane fusion in virus entry: the influenza hem agglutinin. Annu. Rev. Biochem., 2000, 69, 531-569.
12. Durell, S. R.; Martin, I.; Ruysschaert, J. M.; Shai, Y.; Blumenthal, R. What studies of fusion peptides tell us about viral envelope glycoprotein-mediated membrane fusion (review). Mol. Membr. Biol., 1997, 14(3), 97-112.
13. Epand, R. M. Fusion peptides and the mechanism of viral fusion. Biochim. Biophys. Acta, 2003, 1614(1), 116-121.
14. Nieva, J. L.; Agirre, A. Are fusion peptides a good model to study viral cell fusion? Biochim. Biophys. Acta, 2003, 1614(1), 104-115.
15. Shome, S. G.; Kielian, M. Differential roles of two conserved gly-cine residues in the fusion peptide of Semliki Forest virus. Virology, 2001, 279(1), 146-160.
16. Gething, M. J.; Doms, R. W.; York, D.; White, J. Studies on the mechanism of membrane fusion: site-specific mutagenesis of the hem agglutinin of influenza virus. J. Cell Biol., 1986, 102(1), 11-23.
17. Salzwedel, K.; West, J. T.; Hunter, E. A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J. Virol., 1999, 73(3), 2469-2480.
18. Suarez, T.; Gallaher, W. R.; Agirre, A.; Goni, F. M.; Nieva, J. L. Membrane interface-interacting sequences within the ectodomain of the human immunodeficiency virus type 1 envelope glycopro-tein: putative role during viral fusion. J. Virol., 2000, 74 (17), 8038-8047.
19. Saez-Cirion, A.; Arrondo, J. L.; Gomara, M. J.; Lorizate, M.; Iloro, I.; Melikyan, G.; Nieva, J. L. Structural and functional roles of HIV-1 gp41 pretransmembrane sequence segmentation. Biophys. J., 2003, 85(6), 3769-3780.
20. Nieva, J. L.; Suarez, T. Hydrophobic-at-interface regions in viral fusion protein ectodomains. Biosci. Rep., 2000, 20(6), 519-533.
21. Lorizate, M.; Huarte, N.; Saez-Cirion, A.; Nieva, J. L. Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission. Biochim. Biophys. Acta, 2008, 1778(7-8),1624-1639.
22. Wimley, W. C.; White, S. H. Experimentally determined hydro-phobicity scale for proteins at membrane interfaces. Nat. Struct. Biol., 1996, 3(10), 842-848.
23. Haffar, O. K.; Dowbenko, D. J.; Berman, P. W. Topogenic analysis of the human immunodeficiency virus type 1 envelope glycopro-tein, gp160, in microsomal membranes. J. Cell Biol., 1988, 107(5), 1677-1687.
24. Suarez, T.; Nir, S.; Goni, F. M.; Saez-Cirion, A.; Nieva, J. L. The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence. FEBS Lett., 2000, 477(1-2), 145-149.
25. Shnaper, S.; Sackett, K.; Gallo, S. A.; Blumenthal, R.; Shai, Y. The C- and the N-terminal regions of glycoprotein 41 ectodomain fuse membranes enriched and not enriched with cholesterol, respectively. J. Biol. Chem., 2004, 279(18), 18526-18534.
26. Buzon, V.; Natrajan, G.; Schibli, D.; Campelo, F.; Kozlov, M. M.; Weissenhorn, W. Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions. PLoS Pathog., 2010, 6(5), e1000880.
27. Kliger, Y.; Shai, Y. A leucine zipper-like sequence from the cyto-plasmic tail of the HIV-1 envelope glycoprotein binds and perturbs lipid bilayers. Biochemistry, 1997, 36(17), 5157-5169.
28. Costin, J. M.; Rausch, J. M.; Garry, R. F.; Wimley, W. C. Viro-porin potential of the lentivirus lytic peptide (LLP) domains of the HIV-1 gp41 protein. Virol. J., 2007, 4, 123.
29. Nieva, J. L.; Nir, S.; Muga, A.; Goni, F. M.; Wilschut, J. Interaction of the HIV-1 fusion peptide with phospholipid vesicles: different structural requirements for fusion and leakage. Biochemistry, 1994, 33(11), 3201-3209.
30. Pereira, F. B.; Goni, F. M.; Nieva, J. L. Liposome destabilization induced by the HIV-1 fusion peptide effect of a single amino acid substitution. FEBS Lett., 1995, 362(2), 243-246.
31. Kliger, Y.; Aharoni, A.; Rapaport, D.; Jones, P.; Blumenthal, R.; Shai, Y. Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. J. Biol. Chem., 1997, 272(21), 13496-13505.
32. Pereira, F. B.; Goni, F. M.; Muga, A.; Nieva, J. L. Permeabilization and fusion of uncharged lipid vesicles induced by the HIV-1 fusion peptide adopting an extended conformation: dose and sequence effects. Biophys. J., 1997, 73(4), 1977-1986.
33. Pereira, F. B.; Goni, F. M.; Nieva, J. L. Membrane fusion induced by the HIV type 1 fusion peptide: modulation by factors affecting glycoprotein 41 activity and potential anti-HIV compounds. AIDS Res. Hum. Retroviruses, 1997, 13(14), 1203-1211.
34. Agirre, A.; Flach, C.; Goni, F. M.; Mendelsohn, R.; Valpuesta, J. M.; Wu, F.; Nieva, J. L. Interactions of the HIV-1 fusion peptide with large unilamellar vesicles and monolayers. A cryo-TEM and spectroscopic study. Biochim. Biophys. Acta, 2000, 1467(1), 153-164.
35. Yang, J.; Prorok, M.; Castellino, F. J.; Weliky, D. P. Oligomeric beta structure of the membrane-bound HIV-1 fusion peptide formed from soluble monomers. Biophys. J., 2004, 87, 1951-1963.
36. Haque, M. E.; Koppaka, V.; Axelsen, P. H.; Lentz, B. R. Properties and structures of the influenza and HIV fusion peptides on lipid membranes: implications for a role in fusion. Biophys. J., 2005, 89(5), 3183-3194.
37. Li, Y. L.; Tamm, L. K. Structure and plasticity of the human immunodeficiency virus gp41 fusion domain in lipid micelles and bi-layers. Biophys. J., 2007, 93(3), 876-885.
38. Mobley, P. W.; Waring, A. J.; Sherman, M. A.; Gordon, L. M. Membrane interactions of the synthetic N-terminal peptide of HIV-1 gp41 and its structural analogs. Biochim. Biophys. Acta, 1999, 1418(1), 1-18.
39. Siegel, D. P.; Epand, R. M. The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms. Biophys. J., 1997, 73(6), 3089-3111.
40. Siegel, D. P.; Epand, R. M. Effect of influenza hemagglutinin fusion peptide on lamellar/inverted phase transitions in dipalmi-toleoylphosphatidylethanolamine: implications for membrane fusion mechanisms. Biochim. Biophys. Acta, 2000, 1468(1-2), 87-98.
41. Tristram-Nagle, S.; Nagle, J. F. HIV-1 fusion peptide decreases bending energy and promotes curved fusion intermediates. Bio-phys. J., 2007, 93(6), 2048-2055.
42. Qiang, W.; Sun, Y.; Weliky, D. P. A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion pep-tide. Proc. Natl. Acad. Sci. USA, 2009, 106(36), 15314-15319.
43. Schibli, D. J.; Montelaro, R. C.; Vogel, H. J. The membrane-proximal tryptophan-rich region of the HIV glycoprotein, gp41, forms a well-defined helix in dodecylphosphocholine micelles. Biochemistry, 2001, 40(32), 9570-9578.
44. Shnyrova, A. V.; Frolov, V. A.; Zimmerberg, J. Domain-driven morphogenesis of cellular membranes. Curr. Biol., 2009, 19(17), R772-780.
45. Kozlov, M. M. Biophysics: Joint effort bends membrane. Nature, 2010, 463 (7280), 439-440.
46. Chernomordik, L. V.; Kozlov, M. M. Mechanics of membrane fusion. Nat. Struct. Mol. Biol., 2008, 15(7), 675-683.
47. Longo, M. L.; Waring, A. J.; Hammer, D. A. Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation. Biophys. J., 1997, 73(3), 1430-1439.
48. Schneider, S. E.; Bray, B. L.; Mader, C. J.; Friedrich, P. E.; Anderson, M. W.; Taylor, T. S.; Boshernitzan, N.; Niemi, T. E.; Fulcher, B. C.; Whight, S. R.; White, J. M.; Green, R. J.; Stoltenberg, L. E.; Lichty, M. Development of HIV fusion inhibitors. J. Pept. Sci., 2005, 11(11), 744-753.
49. Bosch, M. L.; Earl, P. L.; Fargnoli, K.; Picciafuoco, S.; Giombini, F.; Wong-Staal, F.; Franchini, G. Identification of the fusion pep-tide of primate immunodeficiency viruses. Science, 1989, 244(4905), 694-697.
50. Delahunty, M. D.; Rhee, I.; Freed, E. O.; Bonifacino, J. S. Muta-tional analysis of the fusion peptide of the human immunodeficiency virus type 1: identification of critical glycine residues. Virology, 1996, 218(1), 94-102.
51. Freed, E. O.; Delwart, E. L.; Buchschacher, G. L., Jr.; Panganiban, A. T. A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. Proc. Natl. Acad. Sci. USA, 1992, 89(1), 70-74.
52. Gallaher, W. R. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus. Cell, 1987, 50(3), 327-328.
53. Hernandez, L. D.; Hoffman, L. R.; Wolfsberg, T. G.; White, J. M. Virus-cell and cell-cell fusion. Annu. Rev. Cell Dev. Biol., 1996, 12, 627-661.
54. Longo, M. L.; Waring, A. J.; Gordon, L. M.; Hammer, D. A. Area expansion and permeation of phospholipid membrane bilayers by influenza fusion peptides and melittin. Langmuir, 1998, 14, 2385-2395.
55. Owens, R. J.; Tanner, C. C.; Mulligan, M. J.; Srinivas, R. V.; Com-pans, R. W. Oligopeptide inhibitors of HIV-induced syncytium formation. AIDS Res. Hum. Retroviruses, 1990, 6(11), 1289-1296.
56. Slepushkin, V. A.; Kornilaeva, G. V.; Andreev, S. M.; Sidorova, M. V.; Petrukhina, A. O.; Matsevich, G. R.; Raduk, S. V.; Grigo-riev, V. B.; Makarova, T. V.; Lukashov, V. V. Inhibition of human immunodeficiency virus type 1 (HIV-1) penetration into target cells by synthetic peptides mimicking the N-terminus of the HIV-1 transmembrane glycoprotein. Virology, 1993, 194, (1), 294-301.
57. Pritsker, M.; Jones, P.; Blumenthal, R.; Shai, Y. A synthetic all D-amino acid peptide corresponding to the N-terminal sequence of HIV-1 gp41 recognizes the wild-type fusion peptide in the membrane and inhibits HIV-1 envelope glycoprotein-mediated cell fusion. Proc. Natl. Acad. Sci. USA, 1998, 95(13), 7287-7292.
58. Gerber, D.; Pritsker, M.; Gunther-Ausborn, S.; Johnson, B.; Blu-menthal, R.; Shai, Y. Inhibition of HIV-1 envelope glycoprotein-mediated cell fusion by a DL-amino acid-containing fusion peptide: possible recognition of the fusion complex. J. Biol. Chem., 2004, 279(46), 48224-48230.
59. Munch, J.; Standker, L.; Adermann, K.; Schulz, A.; Schindler, M.; Chinnadurai, R.; Pohlmann, S.; Chaipan, C.; Biet, T.; Peters, T.; Meyer, B.; Wilhelm, D.; Lu, H.; Jing, W.; Jiang, S.; Forssmann, W. G.; Kirchhoff, F. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell, 2007, 129(2), 263-275.
60. Mobley, P. W.; Pilpa, R.; Brown, C.; Waring, A. J.; Gordon, L. M. Membrane-perturbing domains of HIV type 1 glycoprotein 41. AIDS Res. Hum. Retroviruses, 2001, 17(4), 311-327.
61. Forssmann, W. G.; The, Y. H.; Stoll, M.; Adermann, K.; Albrecht, U.; Barlos, K.; Busmann, A.; Canales-Mayordomo, A.; Gimenez-Gallego, G.; Hirsch, J.; Jimenez-Barbero, J.; Meyer-Olson, D.; Munch, J.; Perez-Castells, J.; Standker, L.; Kirchhoff, F.; Schmidt, R. E. Short-term monotherapy in HIV-infected patients with a virus entry inhibitor against the gp41 fusion peptide. Sci. Transl. Med., 2010, 2(63), 63re63.
62. Eckert, D. M.; Malashkevich, V. N.; Hong, L. H.; Carr, P. A.; Kim, P. S. Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell, 1999, 99(1), 103-115.
63. Welch, B. D.; VanDemark, A. P.; Heroux, A.; Hill, C. P.; Kay, M. S. Potent D-peptide inhibitors of HIV-1 entry. Proc. Natl. Acad. Sci. USA, 2007, 104(43), 16828-16833.
64. Houghten, R. A.; Appel, J. R.; Blondelle, S. E.; Cuervo, J. H.; Dooley, C. T.; Pinilla, C. The use of synthetic peptide combinatorial libraries for the identification of bioactive peptides. Biotech-niques, 1992, 13(3), 412-421.
65. Pinilla, C.; Appel, J. R.; Blanc, P.; Houghten, R. A. Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques, 1992, 13(6), 901-905.
66. Lopez-Garcia, B.; Gonzalez-Candelas, L.; Perez-Paya, E.; Marcos, J. F. Identification and characterization of a hexapeptide with activity against phytopathogenic fungi that cause postharvest decay in fruits. Mol. Plant. Microbe. Interact., 2000, 13(8), 837-846.
67. Lopez-Garcia, B.; Perez-Paya, E.; Marcos, J. F. Identification of novel hexapeptides bioactive against phytopathogenic fungi through screening of a synthetic peptide combinatorial library. Appl. Environ. Microbiol., 2002, 68(5), 2453-2460.
68. Blondelle, S. E.; Crooks, E.; Aligue, R.; Agell, N.; Bachs, O.; Esteve, V.; Tejero, R.; Celda, B.; Pastor, M. T.; Perez-Paya, E. Novel, potent calmodulin antagonists derived from an all-D hexapeptide combinatorial library that inhibit in vivo cell proliferation: activity and structural characterization. J. Pept. Res., 2000, 55(2), 148-162.
69. Blondelle, S. E.; Houghten, R. A.; Perez-Paya, E. Identification of inhibitors of melittin using nonsupport-bound combinatorial libraries. J. Biol. Chem., 1996, 271, (8), 4093-4099.
70. Blondelle, S. E.; Houghten, R. A.; Perez-Paya, E. All D-amino acid hexapeptide inhibitors of melittin's cytolytic activity derived from synthetic combinatorial libraries. J. Mol. Recognit., 1996, 9(2), 163-168.
71. Ladokhin, A. S.; Wimley, W. C.; Hristova, K.; White, S. H. Mechanism of leakage of contents of membrane vesicles determined by fluorescence requenching. Methods Enzymol., 1997, 278, 474-486.
72. Nir, S.; Nieva, J. L. Interactions of peptides with liposomes: pore formation and fusion. Prog. Lipid. Res., 2000, 39(2), 181-206.
73. Saez-Cirion, A.; Nieva, J. L. Conformational transitions of membrane-bound HIV-1 fusion peptide. Biochim. Biophys. Acta, 2002, 1564(1), 57-65.
74. Gomara, M. J.; Lorizate, M.; Huarte, N.; Mingarro, I.; Perez-Paya, E.; Nieva, J. L. Hexapeptides that interfere with HIV-1 fusion pep-tide activity in liposomes block GP41-mediated membrane fusion. FEBS Lett., 2006, 580(11), 2561-2566.
75. Blondelle, S. E.; Perez-Paya, E.; Houghten, R. A. Synthetic combinatorial libraries: novel discovery strategy for identification of antimicrobial agents. Antimicrob. Agents Chemother., 1996, 40(5), 1067-1071.
76. Munoz-Barroso, I.; Salzwedel, K.; Hunter, E.; Blumenthal, R. Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion. J. Virol., 1999, 73(7), 6089-6092.
77. Kliger, Y.; Gallo, S. A.; Peisajovich, S. G.; Munoz-Barroso, I.; Avkin, S.; Blumenthal, R.; Shai, Y. Mode of action of an antiviral peptide from HIV-1. Inhibition at a post-lipid mixing stage. J. Biol. Chem., 2001, 276(2), 1391-1397.
78. Saez-Cirion, A.; Nir, S.; Lorizate, M.; Agirre, A.; Cruz, A.; Perez-Gil, J.; Nieva, J. L. Sphingomyelin and cholesterol promote HIV-1 gp41 pretransmembrane sequence surface aggregation and membrane restructuring. J. Biol. Chem., 2002, 277(24), 21776-21785.
79. Aloia, R. C.; Jensen, F. C.; Curtain, C. C.; Mobley, P. W.; Gordon, L. M. Lipid composition and fluidity of the human immunodeficiency virus. Proc. Natl. Acad. Sci. USA, 1988, 85, (3), 900-904.
80. Brügger, B.; Glass, B.; Haberkant, P.; Leibrecht, I.; Wieland, F. T.; Kräusslich, H. G. The HIV lipidome: a raft with an unusual composition. Proc. Natl. Acad. Sci. USA, 2006, 103(8), 2641-2646.
81. Lorizate, M.; Brügger, B.; Akiyama, H.; Glass, B.; Muller, B.; Anderluh, G.; Wieland, F. T.; Kräusslich, H. G. Probing HIV-1 membrane liquid order by Laurdan staining reveals producer cell-dependent differences. J. Biol. Chem., 2009, 284(33), 22238-22247.
82. Nguyen, D. H.; Hildreth, J. E. Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J. Virol., 2000, 74(7), 3264-3272.
83. Campbell, S. M.; Crowe, S. M.; Mak, J. Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectiv-ity. Aids, 2002, 16(17), 2253-2261.
84. Vincent, N.; Genin, C.; Malvoisin, E. Identification of a conserved domain of the HIV-1 transmembrane protein gp41 which interacts with cholesteryl groups. Biochim. Biophys. Acta, 2002, 1567(1-2), 157-164.
85. Epand, R. F.; Sayer, B. G.; Epand, R. M. The tryptophan-rich region of HIV gp41 and the promotion of cholesterol-rich domains. Biochemistry, 2005, 44(14), 5525-5531.
86. Vishwanathan, S. A.; Thomas, A.; Brasseur, R.; Epand, R. F.; Hunter, E.; Epand, R. M. Hydrophobic substitutions in the first residue of the CRAC segment of the gp41 protein of HIV. Biochemistry, 2008, 47(1), 124-130.
87. Chen, S. S.; Yang, P.; Ke, P. Y.; Li, H. F.; Chan, W. E.; Chang, D. K.; Chuang, C. K.; Tsai, Y.; Huang, S. C. Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection. J. Virol., 2009, 83(2), 870-883.
88. Schroeder, C. Cholesterol-binding viral proteins in virus entry and morphogenesis. Subcell. Biochem., 2010, 51, 77-108.
89. Epand, R. F.; Thomas, A.; Brasseur, R.; Vishwanathan, S. A.; Hunter, E.; Epand, R. M. Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains. Biochemistry, 2006, 45(19), 6105-6114.
90. Vishwanathan, S. A.; Thomas, A.; Brasseur, R.; Epand, R. F.; Hunter, E.; Epand, R. M. Large changes in the CRAC segment of gp41 of HIV do not destroy fusion activity if the segment interacts with cholesterol. Biochemistry, 2008, 47(45), 11869-11876.
91. Vishwanathan, S. A.; Hunter, E. Importance of the membrane-perturbing properties of the membrane-proximal external region of human immunodeficiency virus type 1 gp41 to viral fusion. J. Virol., 2008, 82(11), 5118-5126.
92. Lorizate, M.; de la Arada, I.; Huarte, N.; Sanchez-Martinez, S.; de la Torre, B. G.; Andreu, D.; Arrondo, J. L.; Nieva, J. L. Structural analysis and assembly of the HIV-1 Gp41 amino-terminal fusion peptide and the pretransmembrane amphipathic-at-interface sequence. Biochemistry, 2006, 45(48), 14337-14346.
93. Huarte, N.; Lorizate, M.; Maeso, R.; Kunert, R.; Arranz, R.; Valpuesta, J. M.; Nieva, J. L. The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5. J. Virol., 2008, 82(18), 8986-8996.
94. Sun, Z. Y.; Oh, K. J.; Kim, M.; Yu, J.; Brusic, V.; Song, L.; Qiao, Z.; Wang, J. H.; Wagner, G.; Reinherz, E. L. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodo-main region on the viral membrane. Immunity, 2008, 28(1), 52-63.
95. Keating, A. E.; Malashkevich, V. N.; Tidor, B.; Kim, P. S. Side-chain repacking calculations for predicting structures and stabilities of heterodimeric coiled coils. Proc. Natl. Acad. Sci. USA, 2001, 98(26), 14825-14830.
96. Litowski, J. R.; Hodges, R. S. Designing heterodimeric two-stranded alpha-helical coiled-coils. Effects of hydrophobicity and alpha-helical propensity on protein folding, stability, and specificity. J. Biol. Chem., 2002, 277(40), 37272-37279.
97. Park, K.; Perczel, A.; Fasman, G. D. Differentiation between transmembrane helices and peripheral helices by the deconvolution of circular dichroism spectra of membrane proteins. Protein Sci., 1992, 1(8), 1032-1049.
98. Lombardi, S.; Massi, C.; Indino, E.; La Rosa, C.; Mazzetti, P.; Falcone, M. L.; Rovero, P.; Fissi, A.; Pieroni, O.; Bandecchi, P.; Esposito, F.; Tozzini, F.; Bendinelli, M.; Garzelli, C. Inhibition of feline immunodeficiency virus infection in vitro by envelope gly-coprotein synthetic peptides. Virology, 1996, 220(2), 274-284.
99. Giannecchini, S.; Di Fenza, A.; D'Ursi, A. M.; Matteucci, D.; Rovero, P.; Bendinelli, M. Antiviral activity and conformational features of an octapeptide derived from the membrane-proximal ec-todomain of the feline immunodeficiency virus transmembrane glycoprotein. J. Virol., 2003, 77(6), 3724-3733.
100. Giannecchini, S.; Alcaro, M. C.; Isola, P.; Sichi, O.; Pistello, M.; Papini, A. M.; Rovero, P.; Bendinelli, M. Feline immunodeficiency virus plasma load reduction by a retroinverso octapeptide reproducing the Trp-rich motif of the transmembrane glycoprotein. Antivir. Ther., 2005, 10(5), 671-680.
101. Roux, K. H.; Taylor, K. A. AIDS virus envelope spike structure. Curr. Opin. Struct. Biol., 2007, 17(2), 244-252.
102. Campbell, S.; Gaus, K.; Bittman, R.; Jessup, W.; Crowe, S.; Mak, J. The raft-promoting property of virion-associated cholesterol, but not the presence of virion-associated Brij 98 rafts, is a determinant of human immunodeficiency virus type 1 infectivity. J. Virol., 2004, 78(19), 10556-10565.
103. Liao, Z.; Graham, D. R.; Hildreth, J. E. Lipid rafts and HIV patho-genesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS Res. Hum. Retroviruses, 2003, 19(8), 675-687.
104. Zwick, M. B. The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. Aids, 2005, 19(16), 1725-1737.
105. Montero, M.; van Houten, N. E.; Wang, X.; Scott, J. K. The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design. Microbiol. Mol. Biol. Rev., 2008, 72, (1), 54-84.
106. Lorizate, M.; Cruz, A.; Huarte, N.; Kunert, R.; Perez-Gil, J.; Nieva, J. L. Recognition and blocking of HIV-1 gp41 pre-transmembrane sequence by monoclonal 4E10 antibody in a Raft-like membrane environment. J. Biol. Chem., 2006, 281(51), 39598-39606.
107. Huarte, N.; Lorizate, M.; Kunert, R.; Nieva, J. L. Lipid modulation of membrane-bound epitope recognition and blocking by HIV-1 neutralizing antibodies. FEBS Lett., 2008, 582(27), 3798-3804.
108. Apellaniz, B.; Garcia-Saez, A. J.; Huarte, N.; Kunert, R.; Vorauer-Uhl, K.; Katinger, H.; Schwille, P.; Nieva, J. L. Confocal microscopy of giant vesicles supports the absence of HIV-1 neutralizing 2F5 antibody reactivity to plasma membrane phospholipids. FEBS Lett., 2010, 584(8), 1591-1596.
109. Ofek, G.; Tang, M.; Sambor, A.; Katinger, H.; Mascola, J. R.; Wyatt, R.; Kwong, P. D. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J. Virol., 2004, 78(19), 10724-10737.
110. Cardoso, R. M.; Brunel, F. M.; Ferguson, S.; Zwick, M.; Burton, D. R.; Dawson, P. E.; Wilson, I. A. Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10. J. Mol. Biol., 2007, 365(5), 1533-1544.
111. Julien, J. P.; Bryson, S.; Nieva, J. L.; Pai, E. F. Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: Epitope conformation, antigen-recognition loop mobility, and anion-binding site. J. Mol. Biol., 2008, 384, 377-392.
112. Sanchez-Martinez, S.; Lorizate, M.; Katinger, H.; Kunert, R.; Nieva, J. L. Membrane association and epitope recognition by HIV-1 neutralizing anti-gp41 2F5 and 4E10 antibodies. AIDS Res. Hum. Retroviruses, 2006, 22(10), 998-1006.
113. Song, L.; Sun, Z. Y.; Coleman, K. E.; Zwick, M. B.; Gach, J. S.; Wang, J. H.; Reinherz, E. L.; Wagner, G.; Kim, M. Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proc. Natl. Acad. Sci. USA, 2009, 106(22), 9057-9062.
114. Alam, S. M.; Morelli, M.; Dennison, S. M.; Liao, H. X.; Zhang, R.; Xia, S. M.; Rits-Volloch, S.; Sun, L.; Harrison, S. C.; Haynes, B. F.; Chen, B. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc. Natl. Acad. Sci. USA, 2009, 106(48), 20234-20239.
115. Ofek, G.; McKee, K.; Yang, Y.; Yang, Z. Y.; Skinner, J.; Guenaga, F. J.; Wyatt, R.; Zwick, M. B.; Nabel, G. J.; Mascola, J. R.; Kwong, P. D. Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region. J. Virol., 2010, 84(6), 2955-2962.
116. Scherer, E. M.; Leaman, D. P.; Zwick, M. B.; McMichael, A. J.; Burton, D. R. Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions. Proc. Natl. Acad. Sci. USA, 2010, 107(4), 1529-1534.
117. Julien, J. P.; Huarte, N.; Maeso, R.; Taneva, S. G.; Cunningham, A.; Nieva, J. L.; Pai, E. F. Ablation of the complementarity-determining region H3 apex of the anti-HIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding. J. Virol., 2010, 84(9), 4136-4147.
118. Apellaniz, B.; Nir, S.; Nieva, J. L. Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41. Biochemistry, 2009, 48(23), 5320-5331.
119. Oren, Z.; Lerman, J. C.; Gudmundsson, G. H.; Agerberth, B.; Shai, Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem. J., 1999, 341(Pt 3), 501-513.
120. McIntosh, T. J.; Simon, S. A. Bilayers as protein solvents: role of bilayer structure and elastic properties. J. Gen. Physiol., 2007, 130(2), 225-227.
121. Lingwood, D.; Simons, K. Lipid rafts as a membrane-organizing principle. Science, 2010, 327(5961), 46-50.
122. White, S. H.; Wimley, W. C. Membrane protein folding and stability: physical principles. Annu. Rev. Biophys. Biomol. Struct., 1999, 28, 319-365.