Integrin structure, activation, and interactions

Cold Spring Harbor Perspectives in Biology

Volumn 3, Issue 3, 2011, Pages 1-14

  Campbell, Iain D ^a   Humphries, Martin J ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALIA; METAZOA;

CATION; INTEGRIN; LIGAND;

BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; METABOLISM; PHYSIOLOGY; PROTEIN CONFORMATION; PROTEIN TERTIARY STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

BINDING SITES; CATIONS; INTEGRINS; LIGANDS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; SIGNAL TRANSDUCTION;

EID: 84863900703     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a004994     Document Type: Review

References (91)

1. Adair BD, Yeager M. 2002. Three-dimensional model of the human platelet integrin αIIbβ3 based on electron cryomicroscopy and x-ray crystallography. Proc Natl Acad Sci 99: 14059-14064.
2. Adair BD, Xiong JP, Maddock C, Goodman SL, Arnaout MA, Yeager M. 2005. Three-dimensional EM structure of the ectodomain of integrin αVβ3 in a complex with fibronectin. J Cell Biol 168: 1109-1118.
3. Alon R, Dustin ML. 2007. Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen-presenting cells. Immunity 26: 17-27.
4. Alonso JL, Essafi M, Xiong JP, Stehle T, Arnaout MA. 2002. Does the integrin αA domain act as a ligand for its βA domain? Curr Biol 12: R340-R342.
5. Anthis NJ, Wegener KL, Ye F, Kim C, Goult BT, Lowe ED, Vakonakis I, Bate N, Critchley DR, Ginsberg MH, et al. 2009. The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO J 28: 3623-3632.
6. Arnaout MA, Goodman SL, Xiong JP. 2007. Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol 19: 495-507.
7. Arnaout MA, Mahalingam B, Xiong JP. 2005. Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol 21: 381-410.
8. Askari JA, Buckley PA, Mould AP, Humphries MJ. 2009. Linking integrin conformation to function. J Cell Sci 122: 165-170.
9. Askari JA, Tynan CJ, Webb SE, Martin-Fernandez ML, Ballestrem C, Humphries MJ. 2010. Focal adhesions are sites of integrin extension. J Cell Biol 188: 891-903.
10. Barczyk M, Carracedo S, Gullberg D. 2010. Integrins. Cell Tissue Res 339: 269-280.
11. Beglova N, Blacklow SC, Takagi J, Springer TA. 2002. Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat Struct Biol 9: 282-287.
12. Bennett JS, Berger BW, Billings PC. 2009. The structure and function of platelet integrins. J Thromb Haemost 7: 200-205.
13. Berger BW, Kulp DW, Span LM, DeGrado JL, Billings PC, Senes A, Bennett JS, DeGradoWF. 2010. Consensus motif for integrin transmembrane helix association. Proc Natl Acad Sci 107: 703-708.
14. Byron A, Humphries JD, Askari JA, Craig SE, Mould AP, Humphries MJ. 2009. Anti-integrin monoclonal antibodies. J Cell Sci 122 (Pt 22): 4009-4011.
15. Calzada MJ, Alvarez MV, Gonzalez-Rodriguez J. 2002. Agonist-specific structural rearrangements of integrin αIIbβ3. Confirmation of the bent conformation in platelets at rest and after activation. J Biol Chem 277: 39899-39908.
16. Chen J, Salas A, Springer TA. 2003. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nat Struct Biol 10: 995-1001.
17. Chen LL, Whitty A, Lobb RR, Adams SP, Pepinsky RB. 1999. Multiple activation states of integrin α4β1 detected through their different affinities for a small molecule ligand. J Biol Chem 274: 13167-13175.
18. Cheng M, Foo SY, Shi ML, Tang RH, Kong LS, Law SK, Tan SM. 2007. Mutation of a conserved asparagine in the I-like domain promotes constitutively active integrins αLβ2 and αIIbβ3. J Biol Chem 282: 18225-18232.
19. Chigaev A, Buranda T, Dwyer DC, Prossnitz ER, Sklar LA. 2003. FRET detection of cellular α4-integrin conformational activation. Biophys J 85: 3951-3962.
20. Chigaev A, Waller A, Zwartz GJ, Buranda T, Sklar LA. 2007. Regulation of cell adhesion by affinity and conformational unbending of α4β1 integrin. J Immunol 178: 6828-6839.
21. Coller BS. 1985. A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. J Clin Invest 76: 101-108.
22. Critchley DR. 2009. Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annu Rev Biophys 38: 235-254.
23. Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC. 2000. Structural basis of collagen recognition by integrin α2β1. Cell 101: 47-56.
24. Evans EA, Calderwood DA. 2007. Forces and bond dynamics in cell adhesion. Science 316: 1148-1153.
25. Frelinger AL III, Cohen I, Plow EF, Smith MA, Roberts J, Lam SC, Ginsberg MH. 1990. Selective inhibition of integrin function by antibodies specific for ligand-occupied receptor conformers. J Biol Chem 265: 6346-6352.
26. Frelinger AL III, Du XP, Plow EF, Ginsberg MH. 1991. Monoclonal antibodies to ligand-occupied conformers of integrin αIIbβ3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function. J Biol Chem 266: 17106-17111.
27. Gottschalk KE. 2005. A coiled-coil structure of the αIIbβ3 integrin transmembrane and cytoplasmic domains in its resting state. Structure 13: 703-712.
28. Gupta V, Gylling A, Alonso JL, Sugimori T, Ianakiev P, Xiong JP, Arnaout MA. 2007. The β-tail domain (βTD) regulates physiologic ligand binding to integrin CD11b/CD18. Blood 109: 3513-3520.
29. Hanson J, de Leval X, David JL, Supuran C, Pirotte B, Dogne JM. 2004. Progress in the field of GPIIb/IIIa antagonists. Curr Med Chem Cardiovasc Hematol Agents 2: 157-167.
30. Hato T, Yamanouchi J, Yakushijin Y, Sakai I, Yasukawa M. 2006. Identification of critical residues for regulation of integrin activation in the β6-α7 loop of the integrin β3 I-like domain. J Thromb Haemost 4: 2278-2280.
31. Humphries MJ. 2000. Integrin structure. Biochem Soc Trans 28: 311-339.
32. Humphries MJ. 2004. Monoclonal antibodies as probes of integrin priming and activation. Biochem Soc Trans 32: 407-411.
33. Humphries MJ, Symonds EJ, Mould AP. 2003. Mapping functional residues onto integrin crystal structures. Curr Opin Struct Biol 13: 236-243.
34. Huth JR, Olejniczak ET, Mendoza R, Liang H, Harris EA, Lupher ML Jr, Wilson AE, Fesik SW, Staunton DE. 2000. NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding. Proc Natl Acad Sci 97: 5231-5236.
35. Hynes RO. 2002. Integrins: Bidirectional, allosteric signaling machines. Cell 110: 673-687.
36. Hynes RO. 2004. The emergence of integrins: A personal and historical perspective. Matrix Biol 23: 333-340.
37. Ido H, Nakamura A, Kobayashi R, Ito S, Li S, Futaki S, Sekiguchi K. 2007. The requirement of the glutamic acid residue at the third position fromthe carboxyl termini of the laminin g chains in integrin binding by laminins. J Biol Chem 282: 11144-11154.
38. Kallen J, Welzenbach K, Ramage P, GeylD, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U. 1999. Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol 292: 1-9.
39. Keizer GD, Visser W, Vliem M, Figdor CG. 1988. A monoclonal antibody (NKI-L16) directed against a unique epitope on the α-chain of human leukocyte functionassociated antigen 1 induces homotypic cell-cell interactions. J Immunol 140: 1393-1400.
40. Kim M, Carman CV, Springer TA. 2003. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301: 1720-1725.
41. Larson RS, Corbi AL, Berman L, Springer T. 1989. Primary structure of the leukocyte function-associated molecule-1 α subunit: An integrin with an embedded domain defining a protein superfamily. J Cell Biol 108: 703-712.
42. Lau TL, Dua V, Ulmer TS. 2008a. Structure of the integrin αIIb transmembrane segment. J Biol Chem 283: 16162-16168.
43. Lau TL, Kim C, Ginsberg MH, Ulmer TS. 2009. The structure of the integrin αIIbβ3 transmembrane complex explains integrin transmembrane signalling. EMBO J 28: 1351-1361.
44. Lau TL, Partridge AW, Ginsberg MH, Ulmer TS. 2008b. Structure of the integrin β3 transmembrane segment in phospholipid bicelles and detergent micelles. Biochemistry 47: 4008-4016.
45. Lee JO, Bankston LA, Arnaout MA, Liddington RC. 1995a. Two conformations of the integrin A-domain (I-domain): A pathway for activation? Structure 3: 1333-1340.
46. Lee JO, Rieu P, Arnaout MA, Liddington R. 1995b. Crystal structure of the A domain from the α subunit of integrin CR3 (CD11b/CD18). Cell 80: 631-638.
47. Legate KR, Fassler R. 2009. Mechanisms that regulate adaptor binding to β-integrin cytoplasmic tails. J Cell Sci 122: 187-198.
48. Li R, Babu CR, Lear JD, Wand AJ, Bennett JS, DeGrado WF. 2001. Oligomerization of the integrin αIIbβ3: Roles of the transmembrane and cytoplasmic domains. Proc Natl Acad Sci 98: 12462-12467.
49. Li R, Mitra N, Gratkowski H, Vilaire G, Litvinov R, Nagasami C, Weisel JW, Lear JD, DeGrado WF, Bennett JS. 2003. Activation of integrin αIIbβ3 by modulation of transmembrane helix associations. Science 300: 795-798.
50. Loftus JC, Plow EF, Frelinger AL III, D'Souza SE, Dixon D, Lacy J, Sorge J, Ginsberg MH. 1987. Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function. Proc Natl Acad Sci 84: 7114-7118.
51. Luo BH, Carman CV, Springer TA. 2007. Structural basis of integrin regulation and signaling. Annu Rev Immunol 25: 619-647.
52. Luo BH, Springer TA, Takagi J. 2003. Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand. Proc Natl Acad Sci 100: 2403-2408.
53. Luo BH, Takagi J, Springer TA. 2004. Locking the β3 integrin I-like domain into high and low affinity conformations with disulfides. J Biol Chem 279: 10215-10221.
54. McEver RP, Martin MN. 1984. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem 259: 9799-9804.
55. Metcalf DG, KulpDW, Bennett JS, DeGrado WF. 2009. Multiple approaches converge on the structure of the integrin αIIb/β3 transmembrane heterodimer. J Mol Biol 392: 1087-1101.
56. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. 2008. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 14: 325-330.
57. Mould AP, Askari JA, Aota S, Yamada KM, Irie A, Takada Y, Mardon HJ, Humphries MJ. 1997. Defining the topology of integrin α5β1-fibronectin interactions using inhibitory anti-α5 and anti-β1 monoclonal antibodies. Evidence that the synergy sequence of fibronectin is recognized by the amino-terminal repeats of the α5 subunit. J Biol Chem 272: 17283-17292.
58. Mould AP, Barton SJ, Askari JA, Craig SE, Humphries MJ. 2003a. Role of ADMIDAS cation-binding site in ligand recognition by integrin α5β1. J Biol Chem 278: 51622-51629.
59. Mould AP, Barton SJ, Askari JA, McEwan PA, Buckley PA, Craig SE, Humphries MJ. 2003b. Conformational changes in the integrin βA domain provide a mechanism for signal transduction via hybrid domain movement. J Biol Chem 278: 17028-17035.
60. Mould AP, Symond EJ, Buckley PA, Grossmann JG, McEwan PA, Barton SJ, Askari JA, Craig SE, Bella J, Humphries MJ. 2003c. Structure of an integrin-ligand complex deduced from solution x-ray scattering and site-directed mutagenesis. J Biol Chem 278: 39993-39999.
61. Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer TA. 2006. Activation of leukocyte β2 integrins by conversion from bent to extended conformations. Immunity 25: 583-594.
62. Nogales A, Garcia C, Perez J, Callow P, Ezquerra TA, Gonzalez-Rodriguez J. 2010. Three-dimensional model of human platelet integrin αIIbβ3 in solution obtained by small angle neutron scattering. J Biol Chem 285: 1023-1031.
63. Oxvig C, Springer TA. 1998. Experimental support for a β-propeller domain in integrin α-subunits and a calcium binding site on its lower surface. Proc Natl Acad Sci 95: 4870-4875.
64. Parise LV, Helgerson SL, Steiner B, Nannizzi L, Phillips DR. 1987. Synthetic peptides derived from fibrinogen and fibronectin change the conformation of purified platelet glycoprotein IIb-IIIa. J Biol Chem 262: 12597-12602.
65. Parthasarathy K, Lin X, Tan SM, Law SK, Torres J. 2008. Transmembrane helices that form two opposite homodimeric interactions: An asparagine scan study of αM and β2 integrins. Protein Sci 17: 930-938.
66. Partridge AW, Liu S, Kim S, Bowie JU, Ginsberg MH. 2005. Transmembrane domain helix packing stabilizes integrin αIIbβ3 in the low affinity state. J Biol Chem 280: 7294-7300.
67. Plow EF, Haas TA, Zhang L, Loftus J, Smith JW. 2000. Ligand binding to integrins. J Biol Chem 275: 21785-21788.
68. Rocco M, Rosano C, Weisel JW, Horita DA, Hantgan RR. 2008. Integrin conformational regulation: Uncoupling extension/tail separation from changes in the head region by a multiresolution approach. Structure 16: 954-964.
69. Shi M, Sundramurthy K, Liu B, Tan SM, Law SK, Lescar J. 2005. The crystal structure of the plexin-semaphorinintegrin domain/hybrid domain/I-EGF1 segment from the human integrin β2 subunit at 1.8 fangstromg resolution. J Biol Chem 280: 30586-30593.
70. Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, McCormack A, Zhang R, Joachimiak A, Takagi J, et al. 2003. Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell 112: 99-111.
71. Shoemaker BA, Portman JJ, Wolynes PG. 2000. Speeding molecular recognition by using the folding funnel: The fly-casting mechanism. Proc Natl Acad Sci 97: 8868-8873.
72. Sims PJ, Ginsberg MH, Plow EF, Shattil SJ. 1991. Effect of platelet activation on the conformation of the plasma membrane glycoprotein IIb-IIIa complex. J Biol Chem 266: 7345-7352.
73. Takagi J, Petre BM, Walz T, Springer TA. 2002. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110: 599-511.
74. Takagi J, Strokovich K, Springer TA, Walz T. 2003. Structure of integrin α5β1 in complex with fibronectin. EMBO J 22: 4607-4615.
75. Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO. 1986. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 46: 271-282.
76. Ulmer TS, Yaspan B, Ginsberg MH, Campbell ID. 2001. NMR analysis of structure and dynamics of the cytosolic tails of integrin αIIbβ3 in aqueous solution. Biochemistry 40: 7498-7508.
77. van der Flier A, Sonnenberg A. 2001. Function and interactions of integrins. Cell Tissue Res 305: 285-298.
78. Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E, Qin J. 2002. A structural mechanism of integrin αIIbβ3 'inside-out' activation as regulated by its cytoplasmic face. Cell 110: 587-597.
79. Wang W, Luo BH. 2010. Structural basis of integrin transmembrane activation. J Cell Biochem 109: 447-452.
80. Wegener KL, Campbell ID. 2008. Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions. Mol Membr Biol 25: 376-387.
81. Weljie AM, Hwang PM, Vogel HJ. 2002. Solution structures of the cytoplasmic tail complex from platelet integrin αIIb-and β3-subunits. Proc Natl Acad Sci 99: 5878-5883.
82. Xiao T, Takagi J, Coller BS, Wang JH, Springer TA. 2004. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 432: 59-67.
83. Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA. 2009. Structure of an integrin with an αI domain, complement receptor type 4. EMBO J 29: 666-679.
84. Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, Arnaout MA. 2001. Crystal structure of the extracellular segment of integrin αVβ3. Science 294: 339-345.
85. Xiong JP, Stehle T, Goodman SL, Arnaout MA. 2004. A novel adaptation of the integrin PSI domain revealed from its crystal structure. J Biol Chem 279: 40252-40254.
86. Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA. 2002. Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand. Science 296: 151-155.
87. Yang J, Ma YQ, Page RC, Misra S, Plow EF, Qin J. 2009. Structure of an integrin αIIbβ3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation. Proc Natl Acad Sci 106: 17729-17734.
88. Ye F, Hu G, Taylor D, Ratnikov B, Bobkov AA, McLean MA, Sligar SG, Taylor KA, Ginsberg MH. 2010. Recreation of the terminal events in physiological integrin activation. J Cell Biol 188: 157-173.
89. 2+ activation when observed by cryoelectron tomography. J Mol Biol 378: 976-986.
90. Zhu J, Luo BH, Barth P, Schonbrun J, Baker D, Springer TA. 2009. The structure of a receptor with two associating transmembrane domains on the cell surface: Integrin αIIbβ3. Mol Cell 34: 234-249.
91. Zhu J, Luo BH, Xiao T, Zhang C, Nishida N, Springer TA. 2008. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32: 849-861.