Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations

Proteins: Structure, Function and Bioinformatics

Volumn 82, Issue 12, 2014, Pages 3231-3240

  Provasi, Davide ^a   Negri, Ana ^a   Coller, Barry S ^b   Filizola, Marta ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Anton; CHARMM; Long scale MD; Membrane; Molecular complex

Indexed keywords

ALPHA II B BETA 3 INTEGRIN; INTEGRIN; LIPID; TALIN; UNCLASSIFIED DRUG; WATER; FIBRINOGEN RECEPTOR; PEPTIDE FRAGMENT; TLN1 PROTEIN, HUMAN;

ARTICLE; ATOM; CARBOXY TERMINAL SEQUENCE; MOLECULAR DYNAMICS; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN INDUCTION; PROTEIN MOTIF; THROMBOCYTE; BIOLOGICAL MODEL; CELL MEMBRANE; CHEMISTRY; HUMAN; KINETICS; METABOLISM; PROTEIN DATABASE; PROTEIN REFOLDING; PROTEIN STABILITY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SURFACE PROPERTY; THROMBOCYTE ACTIVATION;

CELL MEMBRANE; DATABASES, PROTEIN; HUMANS; KINETICS; MODELS, BIOLOGICAL; MOLECULAR DYNAMICS SIMULATION; PEPTIDE FRAGMENTS; PLATELET ACTIVATION; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PROTEIN CONFORMATION; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN REFOLDING; PROTEIN STABILITY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SURFACE PROPERTIES; TALIN;

EID: 84928104664     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.24540     Document Type: Article

References (49)

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;112:3011-3025.
2. 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;32:849-861.
3. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002;110:673-687.
4. Hu P, Luo BH. Integrin bi-directional signaling across the plasma membrane. J Cell Physiol 2013;228:306-312.
5. 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;188:157-173.
6. Ye F, Kim C, Ginsberg MH. Molecular mechanism of inside-out integrin regulation. J Thromb Haemost 2011;9:20-25.
7. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 2010;11:288-300.
8. Takagi J, Petre BM, Walz T, Springer TA. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 2002;110:599-511.
9. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol 2007;25:619-647.
10. Kim C, Lau TL, Ulmer TS, Ginsberg MH. Interactions of platelet integrin alphaIIb and beta3 transmembrane domains in mammalian cell membranes and their role in integrin activation. Blood 2009;113:4747-4753.
11. Li W, Metcalf DG, Gorelik R, Li R, Mitra N, Nanda V, Law PB, Lear JD, Degrado WF, Bennett JS. A push-pull mechanism for regulating integrin function. Proc Natl Acad Sci USA 2005;102:1424-1429.
12. Luo BH, Carman CV, Takagi J, Springer TA. Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering. Proc Natl Acad Sci USA 2005;102:3679-3684.
13. Luo BH, Springer TA, Takagi J. A specific interface between integrin transmembrane helices and affinity for ligand. PLoS Biol 2004;2:e153.
14. Partridge AW, Liu S, Kim S, Bowie JU, Ginsberg MH. Transmembrane domain helix packing stabilizes integrin alphaIIbbeta3 in the low affinity state. J Biol Chem 2005;280:7294-7300.
15. Wang W, Zhu J, Springer TA, Luo BH. Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling. J Biol Chem 2011;286:1860-1867.
16. Yin H, Slusky JS, Berger BW, Walters RS, Vilaire G, Litvinov RI, Lear JD, Caputo GA, Bennett JS, DeGrado WF. Computational design of peptides that target transmembrane helices. Science 2007;315:1817-1822.
17. Zhu J, Carman CV, Kim M, Shimaoka M, Springer TA, Luo BH. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood 2007;110:2475-2483.
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;286:35218-35226.
19. Kim C, Ye F, Hu X, Ginsberg MH. Talin activates integrins by altering the topology of the beta transmembrane domain. J Cell Biol 2012;197:605-611.
20. Moore DT, Nygren P, Jo H, Boesze-Battaglia K, Bennett JS, DeGrado WF. Affinity of talin-1 for the beta3-integrin cytosolic domain is modulated by its phospholipid bilayer environment. Proc Natl Acad Sci USA 2012;109:793-798.
21. 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 USA 2009;106:17729-17734.
22. Metcalf DG, Moore DT, Wu Y, Kielec JM, Molnar K, Valentine KG, Wand AJ, Bennett JS, DeGrado WF. NMR analysis of the alphaIIb beta3 cytoplasmic interaction suggests a mechanism for integrin regulation. Proc Natl Acad Sci USA 2010;107:22481-22486.
23. Kahner BN, Kato H, Banno A, Ginsberg MH, Shattil SJ, Ye F. Kindlins, integrin activation and the regulation of talin recruitment to alphaIIbbeta3. PLoS One 2012;7:e34056.
24. Kurtz L, Kao L, Newman D, Kurtz I, Zhu Q. Integrin alphaIIbbeta3 inside-out activation: an in situ conformational analysis reveals a new mechanism. J Biol Chem 2012;287:23255-23265.
25. Kalli AC, Wegener KL, Goult BT, Anthis NJ, Campbell ID, Sansom MS. The structure of the talin/integrin complex at a lipid bilayer: an NMR and MD simulation study. Structure 2010;18:1280-1288.
26. Kalli AC, Campbell ID, Sansom MS. Multiscale simulations suggest a mechanism for integrin inside-out activation. Proc Natl Acad Sci USA 2011;108:11890-11895.
27. Mehrbod M, Trisno S, Mofrad MR. On the Activation of Integrin alphaIIbbeta3: outside-in and inside-out pathways. Biophys J 2013;105:1304-1315.
28. Kalli AC, Campbell ID, Sansom MS. Conformational changes in talin on binding to anionic phospholipid membranes facilitate signaling by integrin transmembrane helices. PLoS Comput Biol 2013;9:e1003316.
29. Lau TL, Kim C, Ginsberg MH, Ulmer TS. The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J 2009;28:1351-1361.
30. Shaw DE, Deneroff MM, Dror RO, Kuskin JS, Larson RH, Salmon JK, Young C, Batson B, Bowers KJ, Chao JC, Eastwood MP, Gagliardo J, Grossman JP, Ho CR, Ierardi DJ, Kolossvary I, Klepeis JL, Layman T, McLeavey C, Moraes MA, Mueller R, Priest EC, Shan YB, Spengler J, Theobald M, Towles B, Wang SC. Anton, a special-purpose machine for molecular dynamics simulation. Commun ACM 2008;51:91-97.
31. Anthis NJ, Wegener KL, Ye F, Kim C, Goult BT, Lowe ED, Vakonakis I, Bate N, Critchley DR, Ginsberg MH, Campbell ID. The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO J 2009;28:3623-3632.
32. Lau TL, Dua V, Ulmer TS. Structure of the integrin alphaIIb transmembrane segment. J Biol Chem 2008;283:16162-16168.
33. Mackerell Jr. AD, Bashford D, Bellot M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau TK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich B, Smith J, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Karplus M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 1998;102:3586-3616.
34. Mackerell AD, Jr., Feig M, Brooks CL III. Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem 2004;25:1400-1415.
35. Mezei M, Filizola M. TRAJELIX: a computational tool for the geometric characterization of protein helices during molecular dynamics simulations. J Comput Aided Mol Des 2006;20:97-107.
36. Mezei M. Simulaid: a simulation facilitator and analysis program. J Computat Chem 2010;31:2658-2668.
37. Barth P, Schonbrun J, Baker D. Toward high-resolution prediction and design of transmembrane helical protein structures. Proc Natl Acad Sci USA 2007;104:15682-15687.
38. Barth P, Wallner B, Baker D. Prediction of membrane protein structures with complex topologies using limited constraints. Proc Natl Acad Sci USA 2009;106:1409-1414.
39. Zhu J, Luo BH, Barth P, Schonbrun J, Baker D, Springer TA. The structure of a receptor with two associating transmembrane domains on the cell surface: integrin alphaIIbbeta3. Mol Cell 2009;34:234-249.
40. Hughes PE, Diaz-Gonzalez F, Leong L, Wu C, McDonald JA, Shattil SJ, Ginsberg MH. Breaking the integrin hinge. A defined structural constraint regulates integrin signaling. J Biol Chem 1996;271:6571-6574.
41. Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E, Qin J. A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face. Cell 2002;110:587-597.
42. Armulik A, Nilsson I, von Heijne G, Johansson S. Determination of the border between the transmembrane and cytoplasmic domains of human integrin subunits. J Biol Chem 1999;274:37030-37034.
43. Stefansson A, Armulik A, Nilsson I, von Heijne G, Johansson S. Determination of N- and C-terminal borders of the transmembrane domain of integrin subunits. J Biol Chem 2004;279:21200-21205.
44. Lau TL, Partridge AW, Ginsberg MH, Ulmer TS. Structure of the integrin beta3 transmembrane segment in phospholipid bicelles and detergent micelles. Biochemistry 2008;47:4008-4016.
45. Calderwood DA, Yan B, de Pereda JM, Alvarez BG, Fujioka Y, Liddington RC, Ginsberg MH. The phosphotyrosine binding-like domain of talin activates integrins. J Biol Chem 2002;277:21749-21758.
46. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 2008;14:325-330.
47. Harburger DS, Bouaouina M, Calderwood DA. Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects. J Biol Chem 2009;284:11485-11497.
48. Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 2003;301:1720-1725.
49. Williams MJ, Hughes PE, O'Toole TE, Ginsberg MH. The inner world of cell adhesion: integrin cytoplasmic domains. Trends Cell Biol 1994;4:109-112.