αIIbβ3: Structure and function

Journal of Thrombosis and Haemostasis

Volumn 13, Issue S1, 2015, Pages S17-S25

  Coller, B S ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Electron microscopy; Integrin alphaIIbbeta3; Platelet; Thrombosis; X ray crystallography

Indexed keywords

ABCIXIMAB; ALPHA2BBETA3 INTEGRIN; CALCIUM ION; DETERGENT; EPTIFIBATIDE; FIBRINOGEN RECEPTOR ANTAGONIST; FIBRONECTIN; INTEGRIN RECEPTOR; MAGNESIUM ION; METAL ION; RUC 1; RUC 2; RUC 4; TIROFIBAN; UNCLASSIFIED DRUG; UR 3216; VITRONECTIN RECEPTOR; ANTITHROMBOCYTIC AGENT; FIBRINOGEN RECEPTOR; LIGAND; PROTEIN BINDING;

ADJACENT TO METAL ION DEPENDENT ADHESION SITE; BINDING SITE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DRUG EFFICACY; DRUG MECHANISM; DRUG RECEPTOR BINDING; HUMAN; INTRACELLULAR SIGNALING; LIGAND BINDING; LIPID BILAYER; METAL ION DEPENDENT ADHESION SITE; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; RECEPTOR BLOCKING; RECEPTOR INTRINSIC ACTIVITY; REVIEW; SYNERGISTIC METAL ION BINDING SITE; THROMBOCYTE AGGREGATION; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG EFFECTS; HEMOSTASIS; METABOLISM; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; THROMBOCYTE;

ANIMALS; BINDING SITES; BLOOD PLATELETS; DRUG DESIGN; HEMOSTASIS; HUMANS; LIGANDS; MODELS, MOLECULAR; PLATELET AGGREGATION INHIBITORS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PROTEIN BINDING; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84931294411     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12915     Document Type: Review

References (66)

1. Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008; 112: 3011-25.
2. Bosch X, Marrugat J, Sanchis J. Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention and as the initial medical treatment of non-ST segment elevation acute coronary syndromes. Cochrane Database Syst Rev 2013; 11: CD002130.
3. Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol 2013; 161: 3-14.
4. Zhu J, Luo BH, Xiao T, Zhang C, Nishida N, Springer TA. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 2008; 32: 849-61.
5. Xiao T, Takagi J, Coller BS, Wang J, Springer TA. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 2004; 432: 59-67.
6. Zhu J, Zhu J, Negri A, Provasi D, Filizola M, Coller BS, Springer TA. Closed headpiece of integrin αIIbβ3 and its complex with an αIIbβ3-specific antagonist that does not induce opening. Blood 2010; 116: 5050-9.
7. Springer TA, Zhu J, Xiao T. Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3. J Cell Biol 2008; 182: 791-800.
8. Zhu J, Zhu J, Springer TA. Complete integrin headpiece opening in eight steps. J Cell Biol 2013; 201: 1053-68.
9. Kim C, Schmidt T, Cho EG, Ye F, Ulmer TS, Ginsberg MH. Basic amino-acid side chains regulate transmembrane integrin signalling. Nature 2012; 481: 209-13.
10. Yang J, Ma YQ, Page RC, Misra S, Plow EF, Qin J. Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation. Proc Natl Acad Sci U S A 2009; 106: 17729-34.
11. Ma YQ, Yang J, Pesho MM, Vinogradova O, Qin J, Plow EF. Regulation of integrin alphaIIbbeta3 activation by distinct regions of its cytoplasmic tails. Biochemistry 2006; 45: 6656-62.
12. Huang H, Vogel HJ. Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1. J Am Chem Soc 2012; 134: 3864-72.
13. Carrell NA, Fitzgerald LA, Steiner B, Erickson HP, Phillips DR. Structure of human platelet membrane glycoproteins IIb and IIIa as determined by electron microscopy. J Biol Chem 1985; 260: 1743-9.
14. Weisel JW, Nagaswami C, Vilaire G, Bennett JS. Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. J Biol Chem 1992; 267: 16637-43.
15. Du X, Gu M, Weisel JW, Nagaswami C, Bennett JS, Bowditch R, Ginsberg MH. Long range propagation of conformational changes in integrin alpha IIb beta 3. J Biol Chem 1993; 268: 23087-92.
16. Adair BD, Yeager M. Three-dimensional model of the human platelet integrin alpha IIbbeta 3 based on electron cryomicroscopy and x-ray crystallography. Proc Natl Acad Sci USA 2002; 99: 14059-64.
17. Nogales A, Garcia C, Perez J, Callow P, Ezquerra TA, Gonzalez-Rodriguez J. Three-dimensional model of human platelet integrin alphaIIb beta3 in solution obtained by small angle neutron scattering. J Biol Chem 2010; 285: 1023-31.
18. Eng ET, Smagghe BJ, Walz T, Springer TA. Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy. J Biol Chem 2011; 286: 35218-26.
19. Ye F, Hu G, Taylor D, Ratnikov B, Bobkov AA, McLean MA, Sligar SG, Taylor KA, Ginsberg MH. Recreation of the terminal events in physiological integrin activation. J Cell Biol 2010; 188: 157-73.
20. Iwasaki K, Mitsuoka K, Fujiyoshi Y, Fujisawa Y, Kikuchi M, Sekiguchi K, Yamada T. Electron tomography reveals diverse conformations of integrin alphaIIbbeta3 in the active state. J Struct Biol 2005; 150: 259-67.
21. 2+ binding to the MIDAS. Sci Transl Med 2012; 4: 1-12.
22. Choi WS, Rice WJ, Stokes DL, Coller BS. Three-dimensional reconstruction of intact human integrin alphaIIbbeta3: new implications for activation-dependent ligand binding. Blood 2013; 122: 4165-71.
23. Donald JE, Zhu H, Litvinov RI, DeGrado WF, Bennett JS. Identification of interacting hot spots in the beta3 integrin stalk using comprehensive interface design. J Biol Chem 2010; 285: 38658-65.
24. Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA. Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand. Science 2002; 296: 151-5.
25. Bennett JS, Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest 1979; 64: 1393-401.
26. Vorup-Jensen T, Waldron TT, Astrof N, Shimaoka M, Springer TA. The connection between metal ion affinity and ligand affinity in integrin I domains. Biochim Biophys Acta 2007; 1774: 1148-55.
27. Honda S, Tomiyama Y, Aoki T, Shiraga M, Kurata Y, Seki J, Matsuzawa Y. Association between ligand-induced conformational changes of integrin IIbbeta3 and IIbbeta3-mediated intracellular Ca2+ signaling. Blood 1998; 92: 3675-83.
28. van Agthoven JF, Xiong JP, Alonso JL, Rui X, Adair BD, Goodman SL, Arnaout MA. Structural basis for pure antagonism of integrin alphaVbeta3 by a high-affinity form of fibronectin. Nat Struct Mol Biol 2014; 21: 383-8.
29. Murcia M, Jirouskova M, Li J, Coller BS, Filizola M. Functional and computational studies of the ligand-associated metal binding site of beta3 integrins. Proteins 2008; 71: 1779-91.
30. Dong X, Hudson NE, Lu C, Springer TA. Structural determinants of integrin beta-subunit specificity for latent TGF-beta. Nat Struct Mol Biol 2014; 21: 1091-6.
31. Dong X, Mi LZ, Zhu J, Wang W, Hu P, Luo BH, Springer TA. alpha(V)beta(3) integrin crystal structures and their functional implications. Biochemistry 2012; 51: 8814-28.
32. Rui X, Mehrbod M, van Agthoven JF, Anand S, Xiong JP, Mofrad MR, Arnaout MA. The alpha-subunit regulates stability of the metal ion at the ligand-associated metal ion-binding site in beta3 integrins. J Biol Chem 2014; 289: 23256-63.
33. Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, Arnaout MA. Crystal structure of the extracellular segment of integrin alphaVbeta3. Science 2001; 294: 339-45.
34. Kloczewiak M, Timmons S, Bednarek MA, Sakon M, Hawiger J. Platelet receptor recognition domain on the gamma chain of human fibrinogen and its synthetic peptide analogues. Biochemistry 1989; 28: 2915-9.
35. Raborn J, Luo BH. Mutagenesis studies of the beta I domain metal ion binding sites on integrin alphaVbeta3 ligand binding affinity. J Cell Biochem 2012; 113: 1190-7.
36. Raborn J, Fu T, Wu X, Xiu Z, Li G, Luo BH. Variation in one residue associated with the metal ion-dependent adhesion site regulates alphaIIbbeta3 integrin ligand binding affinity. PLoS One 2013; 8: e76793.
37. Hu DD, Barbas CF, Smith JW. An allosteric Ca2+ binding site on the beta3-integrins that regulates the dissociation rate for RGD ligands. J Biol Chem 1996; 271: 21745-51.
38. Kunicki TJ, Annis DS, Felding-Habermann B. Molecular determinants of arg-gly-asp ligand specificity for beta3 integrins. J Biol Chem 1997; 272: 4103-7.
39. Xia W, Springer TA. Metal ion and ligand binding of integrin alpha5beta1. Proc Natl Acad Sci U S A 2014; 111: 17863-8.
40. Goodman TG, Bajt ML. Identifying the putative metal ion-dependent adhesion site in the beta2 (CD18) subunit required for alphaLbeta2 and alphaMbeta2 ligand interactions. J Biol Chem 1996; 271: 23729-36.
41. Chen J, Salas A, Springer TA. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nat Struct Biol 2003; 10: 995-1001.
42. Chen J, Takagi J, Xie C, Xiao T, Luo BH, Springer TA. The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7. J Biol Chem 2004; 279: 55556-61.
43. Park EJ, Mora JR, Carman CV, Chen J, Sasaki Y, Cheng G, von Andrian UH, Shimaoka M. Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. J Clin Invest 2007; 117: 2526-38.
44. Kamata T, Tieu KK, Tarui T, Puzon-McLaughlin W, Hogg N, Takada Y. The role of the CPNKEKEC sequence in the beta(2) subunit I domain in regulation of integrin alpha(L)beta(2) (LFA-1). J Immunol 2002; 168: 2296-301.
45. Mould AP, Barton SJ, Askari JA, Craig SE, Humphries MJ. Role of ADMIDAS cation-binding site in ligand recognition by integrin alpha 5 beta 1. J Biol Chem 2003; 278: 51622-9.
46. Tozer EC, Liddington RC, Sutcliffe MJ, Smeeton AH, Loftus JC. Ligand binding to integrin alphaIIbbeta3 is dependent on a MIDAS-like domain in the beta3 subunit. J Biol Chem 1996; 271: 21978-84.
47. Bajt ML, Loftus JC. Mutation of a ligand binding domain of beta 3 integrin. Integral role of oxygenated residues in alpha IIb beta 3 (GPIIb-IIIa) receptor function. J Biol Chem 1994; 269: 20913-9.
48. Pesho MM, Bledzka K, Michalec L, Cierniewski CS, Plow EF. The specificity and function of the metal-binding sites in the integrin beta3 A-domain. J Biol Chem 2006; 281: 23034-41.
49. Cheresh DA, Berliner SA, Vicente V, Ruggeri ZM. Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells. Cell 1989; 58: 945-53.
50. Cox D. Oral GPIIb/IIIa antagonists: what went wrong? Curr Pharm Des 2004; 10: 1587-96.
51. Chew DP, Bhatt DL, Topol EJ. Oral glycoprotein IIb/IIIa inhibitors: why don't they work? Am J Cardiovasc Drugs 2001; 1: 421-8.
52. Brassard JA, Curtis BR, Cooper RA, Ferguson J, Komocsar W, Ehardt M, Kupfer S, Maurath C, Swabb E, Cannon CP, Aster RH. Acute thrombocytopenia in patients treated with the oral glycoprotein IIb/IIIa inhibitors xemilofiban and orbofiban: evidence for an immune etiology. Thromb Haemost 2002; 88: 892-7.
53. Aster RH, Curtis BR, Bougie DW, Dunkley S, Greinacher A, Warkentin TE, Chong BH. Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors. J Thromb Haemost 2006; 4: 678-9.
54. Scirica BM, Cannon CP, Cooper R, Aster RH, Brassard J, McCabe CH, Charlesworth A, Skene AM, Braunwald E. Drug-induced thrombocytopenia and thrombosis: evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes-(OPUS-TIMI 16) trial. J Thromb Thrombolysis 2006; 22: 95-102.
55. Bassler N, Loeffler C, Mangin P, Yuan Y, Schwarz M, Hagemeyer CE, Eisenhardt SU, Ahrens I, Bode C, Jackson SP, Peter K. A mechanistic model for paradoxical platelet activation by ligand-mimetic alphaIIb beta3 (GPIIb/IIIa) antagonists. Arterioscler Thromb Vasc Biol 2007; 27: e9-15.
56. Hantgan RR, Stahle MC. Integrin priming dynamics: mechanisms of integrin antagonist-promoted alphaIIbbeta3:PAC-1 molecular recognition. Biochemistry 2009; 48: 8355-65.
57. Blue R, Murcia M, Karan C, Jirouskova M, Coller BS. Application of high throughput screening to identify a novel αIIb-specific small molecule inhibitor of αIIbβ3-mediated platelet interaction with fibrinogen. Blood 2008; 111: 1248-56.
58. Aga Y, Baba K, Tam S, Nakanishi T, Yoneda K, Kita J, Ueno H. UR-3216: a new generation oral platelet GPIIb/IIIa antagonist. Curr Pharm Des 2004; 10: 1597-601.
59. Cox D, Brennan M, Moran N. Integrins as therapeutic targets: lessons and opportunities. Nat Rev Drug Discov 2010; 9: 804-20.
60. Schwarz M, Rottgen P, Takada Y, Le Gall F, Knackmuss S, Bassler N, Buttner C, Little M, Bode C, Peter K. Single-chain antibodies for the conformation-specific blockade of activated platelet integrin alphaIIbbeta3 designed by subtractive selection from naive human phage libraries. FASEB J 2004; 18: 1704-6.
61. Schwarz M, Meade G, Stoll P, Ylanne J, Bassler N, Chen YC, Hagemeyer CE, Ahrens I, Moran N, Kenny D, Fitzgerald D, Bode C, Peter K. Conformation-specific blockade of the integrin GPIIb/IIIa: a novel antiplatelet strategy that selectively targets activated platelets. Circ Res 2006; 99: 25-33.
62. Blue R, Kowalska MA, Hirsch J, Murcia M, Janczak CA, Harrington A, Jirouskova M, Li J, Fuentes R, Thornton MA, Filizola M, Poncz M, Coller BS. Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel αIIb-specific αIIbβ3 antagonist. Blood 2009; 114: 195-201.
63. Li J, Vootukuri S, Shang Y, Negri A, Jiang JK, Nedelman MA, Diacovo TG, Filizola M, Thomas CJ, Coller BS. RUC-4: a novel αIIbβ3 antagonist for pre-hospital therapy of myocardial infarction. Arterioscler Thromb Vasc Biol 2014; 34: 2321-9.
64. Ye F, Snider AK, Ginsberg MH. Talin and kindlin: the one-two punch in integrin activation. Front Med 2014; 8: 6-16.
65. Das M, Subbayya IS, Qin J, Plow EF. Mechanisms of talin-dependent integrin signaling and crosstalk. Biochim Biophys Acta 2014; 1838: 579-88.
66. Provasi D, Negri A, Coller BS, Filizola M. Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations. Proteins 2014; 82: 3231-40.