αIIbβ3 variants defined by next-generation sequencing: Predicting variants likely to cause Glanzmann thrombasthenia

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 15, 2015, Pages E1898-E1907

  Buitrago, Lorena ^a   Rendon, Augusto ^b,c,d,g   Liang, Yupu ^a   Simeoni, Ilenia ^b,d   Negri, Ana ^e   Filizola, Marta ^e   Ouwehand, Willem H ^b,d,f   Coller, Barry S ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d NHS BLOOD AND TRANSPLANT   (United Kingdom)

^e MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^f WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^g GENOMICS ENGLAND   (United Kingdom)

Author keywords

Glanzmann; Integrin; Molecular modeling; Next generation sequencing; Single nucleotide variants

Indexed keywords

ALLOANTIGEN; FIBRINOGEN; INTEGRIN ALPHA IIB BETA 3 RECEPTOR; INTEGRIN RECEPTOR; UNCLASSIFIED DRUG; FIBRINOGEN RECEPTOR; PROTEIN BINDING;

ALLELE; AMINO ACID SUBSTITUTION; ANISOTHROMBOCYTOPENIA; ARTICLE; CELL LYSATE; CONTROLLED STUDY; DATA BASE; EXOME; FLOW CYTOMETRY; GENE EXPRESSION; GENE FREQUENCY; GENETIC VARIABILITY; GLANZMANN DISEASE; HEK293 CELL LINE; HUMAN; IMMUNOBLOTTING; LIGAND BINDING; MISSENSE MUTATION; MOLECULAR MODEL; NEONATAL ALLOIMMUNE THROMBOCYTOPENIA; NEXT GENERATION SEQUENCING; PHENOTYPE; PREDICTION; PRIORITY JOURNAL; PROTEIN BINDING; THROMBOCYTOPENIA; CHEMISTRY; GENETICS; HIGH THROUGHPUT SEQUENCING; METABOLISM; NUCLEIC ACID DATABASE; PROCEDURES; PROTEIN CONFORMATION; PROTEIN TERTIARY STRUCTURE;

ALLELES; DATABASES, NUCLEIC ACID; EXOME; FIBRINOGEN; GENE FREQUENCY; HEK293 CELLS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; IMMUNOBLOTTING; MODELS, MOLECULAR; MUTATION, MISSENSE; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; THROMBASTHENIA;

EID: 84928161936     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1422238112     Document Type: Article

References (90)

1. Koboldt DC, Steinberg KM, Larson DE, Wilson RK, Mardis ER (2013) The next-generation sequencing revolution and its impact on genomics. Cell 155(1):27-38.
2. Tennessen JA, et al.; Broad GO; Seattle GO; NHLBI Exome Sequencing Project (2012) Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337(6090):64-69.
3. Nelson MR, et al. (2012) An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people. Science 337(6090):100-104.
4. Coller BS, Shattil SJ (2008) The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: A technology-driven saga of a receptor with twists, turns, and even a bend. Blood 112(8):3011-3025.
5. Coller BS, Seligsohn U, Peretz H, Newman PJ (1994) Glanzmann thrombasthenia: New insights from an historical perspective. Semin Hematol 31(4):301-311.
6. Nurden AT, Fiore M, Nurden P, Pillois X (2011) Glanzmann thrombasthenia: A review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 118(23):5996-6005.
7. Caen JP, et al. (1966) Congenital bleeding disorders with long bleeding time and normal platelet count. I. Glanzmanns thrombasthenia (report of 15 patients). Am J Med 41(1):4-26.
8. Nurden AT, Caen JP (1974) An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia. Br J Haematol 28(2):253-260.
9. Phillips DR, Agin PP (1977) Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 60(3):535-545.
10. French DL, Seligsohn U (2000) Platelet glycoprotein IIb/IIIa receptors and Glanzmann's thrombasthenia. Arterioscler Thromb Vasc Biol 20(3):607-610.
11. Negri A, Li J, Naini S, Coller BS, Filizola M (2012) Structure-based virtual screening of small-molecule antagonists of platelet integrin αIIbβ3 that do not prime the receptor to bind ligand. J Comput Aided Mol Des 26(9):1005-1015.
12. Provasi D, Negri A, Coller BS, Filizola M (2014) Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations. Proteins 82(12):3231-3240.
13. 2+ binding to the MIDAS. Sci Transl Med 4(125):125ra132.
14. Zhu J, et al. (2010) Closed headpiece of integrin αIIbß3 and its complex with an αIIbβ3-specific antagonist that does not induce opening. Blood 116(23):5050-5059.
15. Murcia M, Jirouskova M, Li J, Coller BS, Filizola M (2008) Functional and computational studies of the ligand-associated metal binding site of beta3 integrins. Proteins 71(4):1779-1791.
16. Filizola M, Hassan SA, Artoni A, Coller BS, Weinstein H (2004) Mechanistic insights from a refined three-dimensional model of integrin alphaIIbbeta3. J Biol Chem 279(23):24624-24630.
17. Choi WS, Rice WJ, Stokes DL, Coller BS (2013) Three-dimensional reconstruction of intact human integrin αIIbβ3: New implications for activation-dependent ligand binding. Blood 122(26):4165-4171.
18. Zhu J, et al. (2008) Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32(6):849-861.
19. Eng ET, Smagghe BJ, Walz T, Springer TA (2011) Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy. J Biol Chem 286(40):35218-35226.
20. 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(7013):59-67.
21. Provasi D, Murcia M, Coller BS, Filizola M (2009) Targeted molecular dynamics reveals overall common conformational changes upon hybrid domain swing-out in beta3 integrins. Proteins 77(2):477-489.
22. Rosenberg N, et al. (1997) Glanzmann thrombasthenia caused by an 11.2-kb deletion in the glycoprotein IIIa (beta3) is a second mutation in Iraqi Jews that stemmed from a distinct founder. Blood 89(10):3654-3662.
23. Rosenberg N, et al. (2005) A 13-bp deletion in alpha(IIb) gene is a founder mutation that predominates in Palestinian-Arab patients with Glanzmann thrombasthenia. J Thromb Haemost 3(12):2764-2772.
24. Fiore M, Pillois X, Nurden P, Nurden AT, Austerlitz F (2011) Founder effect and estimation of the age of the French Gypsy mutation associated with Glanzmann thrombasthenia in Manouche families. Eur J Hum Genet 19(9):981-987.
25. Seligsohn U, Rososhansky S (1984) A Glanzmann's thrombasthenia cluster among Iraqi Jews in Israel. Thromb Haemost 52(3):230-231.
26. Khanduri U, et al. (1981) Glanzmann's thrombasthenia. A review and report of 42 cases from South India. Thromb Haemost 46(4):717-721.
27. Schlegel N, et al. (1995) The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy population in France: Identification of a new mutation on the alpha IIb gene. Blood 86(3):977-982.
28. Awidi AS (1992) Rare inherited bleeding disorders secondary to coagulation factors in Jordan: A nine-year study. Acta Haematol 88(1):11-13.
29. French DL, Coller BS (1997) Hematologically important mutations: Glanzmann thrombasthenia. Blood Cells Mol Dis 23(1):39-51.
30. Nurden AT, Pillois X, Nurden P (2012) Understanding the genetic basis of Glanzmann thrombasthenia: Implications for treatment. Expert Rev Hematol 5(5):487-503.
31. Peterson JA, McFarland JG, Curtis BR, Aster RH (2013) Neonatal alloimmune thrombocytopenia: Pathogenesis, diagnosis and management. Br J Haematol 161(1):3-14.
32. Kashiwagi H, et al. (2013) Demonstration of novel gain-of-function mutations of αIIbβ3: Association with macrothrombocytopenia and Glanzmann thrombasthenia-like phenotype. Mol Genet Genomic Med 1(2):77-86.
33. Kunishima S, et al. (2011) Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia. Blood 117(20):5479-5484.
34. Ghevaert C, et al. (2008) A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the alphaIIbbeta3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia. Blood 111(7):3407-3414.
35. Nurden AT, Pillois X, Fiore M, Heilig R, Nurden P (2011) Glanzmann thrombasthenia-like syndromes associated with macrothrombocytopenias and mutations in the genes encoding the αIIbβ3 integrin. Semin Thromb Hemost 37(6):698-706.
36. Peyruchaud O, et al. (1998) R to Q amino acid substitution in the GFFKR sequence of the cytoplasmic domain of the integrin IIb subunit in a patient with a Glanzmann's thrombasthenia-like syndrome. Blood 92(11):4178-4187.
37. Schaffner-Reckinger E, et al. (2009) Overexpression of the partially activated alpha (IIb)beta3D723H integrin salt bridge mutant downregulates RhoA activity and induces microtubule-dependent proplatelet-like extensions in Chinese hamster ovary cells. J Thromb Haemost 7(7):1207-1217.
38. Jayo A, et al. (2010) L718P mutation in the membrane-proximal cytoplasmic tail of beta 3 promotes abnormal alpha IIb beta 3 clustering and lipid microdomain coalescence, and associates with a thrombasthenia-like phenotype. Haematologica 95(7):1158-1166.
39. Bledzka K, Smyth SS, Plow EF (2013) Integrin αIIbβ3: From discovery to efficacious therapeutic target. Circ Res 112(8):1189-1200.
40. Bosch X, Marrugat J, Sanchis J (2013) 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 11:CD002130.
41. Cox D, Brennan M, Moran N (2010) Integrins as therapeutic targets: Lessons and opportunities. Nat Rev Drug Discov 9(10):804-820.
42. Hynes RO (2002) Integrins: Bidirectional, allosteric signaling machines. Cell 110(6):673-687.
43. Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8(8):604-617.
44. Bennett JS, Berger BW, Billings PC (2009) The structure and function of platelet integrins. J Thromb Haemost 7(Suppl 1):200-205.
45. Du X, Ginsberg MH (1997) Integrin alpha IIb beta 3 and platelet function. Thromb Haemost 78(1):96-100.
46. Mor-Cohen R, et al. (2012) Unique disulfide bonds in epidermal growth factor (EGF) domains of β3 affect structure and function of αIIbβ3 and αvβ3 integrins in different manner. J Biol Chem 287(12):8879-8891.
47. Jallu V, Poulain P, Fuchs PF, Kaplan C, de Brevern AG (2012) Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: Effects on the structure of the β3 subunit of the αIIbβ3 integrin. PLoS ONE 7(11):e47304.
48. Mehrbod M, Trisno S, Mofrad MR (2013) On the activation of integrin αIIbβ3: Outside-in and inside-out pathways. Biophys J 105(6):1304-1315.
49. Laguerre M, et al. (2013) Molecular dynamics analysis of a novel β3 Pro189Ser mutation in a patient with Glanzmann thrombasthenia differentially affecting αIIbβ3 and αvβ3 expression. PLoS ONE 8(11):e78683.
50. Blue R, et al. (2010) Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3. J Biol Chem 285(23):17604-17613.
51. Vomund AN, Stuhlsatz-Krouper S, Dimitry J, Song Y, Frazier WA (2008) A naturally occurring extracellular alpha-beta clasp contributes to stabilization of beta3 integrins in a bent, resting conformation. Biochemistry 47(44):11616-11624.
52. Levin L, et al. (2013) A single disulfide bond disruption in the β3 integrin subunit promotes thiol/disulfide exchange, a molecular dynamics study. PLoS ONE 8(3):e59175.
53. Kamata T, et al. (2010) Structural requirements for activation in alphaIIb beta3 integrin. J Biol Chem 285(49):38428-38437.
54. Valdar WS, Thornton JM (2001) Protein-protein interfaces: Analysis of amino acid conservation in homodimers. Proteins 42(1):108-124.
55. Valdar WS (2002) Scoring residue conservation. Proteins 48(2):227-241.
56. Sievers F, et al. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539.
57. Kircher M, et al. (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46(3):310-315.
58. Adzhubei IA, et al. (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248-249.
59. Ng PC, Henikoff S (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31(13):3812-3814.
60. Losonczy G, et al. (2007) Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia. Haematologica 92(5):698-701.
61. Wright S (1937) The distribution of gene frequencies in populations. Proc Natl Acad Sci USA 23(6):307-320.
62. Basani RB, et al. (2000) A naturally occurring mutation near the amino terminus of alphaIIb defines a new region involved in ligand binding to alphaIIbbeta3. Blood 95(1):180-188.
63. D'Andrea G, et al.; GLAnzmann's Thrombasthenia Italian Team (GLATIT) (2002) Glanzmann's thrombasthenia: Identification of 19 new mutations in 30 patients. Thromb Haemost 87(6):1034-1042.
64. Nair S, Ghosh K, Shetty S, Mohanty D (2005) Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patients. J Thromb Haemost 3(3):482-488.
65. Vinciguerra C, et al. (2001) Description of 10 new mutations in platelet glycoprotein IIb (alphaIIb) and glycoprotein IIIa (beta3) genes. Platelets 12(8):486-495.
66. Coller BS, et al. (1986) Immunologic and biochemical characterization of homozygous and heterozygous Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations of Israel: Comparison of techniques for carrier detection. Br J Haematol 62(4):723-735.
67. Keinan A, Clark AG (2012) Recent explosive human population growth has resulted in an excess of rare genetic variants. Science 336(6082):740-743.
68. Coventry A, et al. (2010) Deep resequencing reveals excess rare recent variants consistent with explosive population growth. Nat Commun 1:131.
69. Schmitt MW, et al. (2012) Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci USA 109(36):14508-14513.
70. Browning BL, Browning SR (2013) Detecting identity by descent and estimating genotype error rates in sequence data. Am J Hum Genet 93(5):840-851.
71. Schafer CM, et al. (2013) Whole exome sequencing reveals minimal differences between cell line and whole blood derived DNA. Genomics 102(4):270-277.
72. Coller BS, Folts JD, Smith SR, Scudder LE, Jordan R (1989) Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors. Circulation 80(6):1766-1774.
73. Wagner CL, et al. (1996) Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 88(3):907-914.
74. Reichert N, Seligsohn U, Ramot B (1975) Clinical and genetic aspects of Glanzmann's thrombasthenia in Israel: Report of 22 cases. Thromb Diath Haemorrh 34(3):806-820.
75. Cronberg S, Nilsson IM, Zetterqvist E (1967) Investigation of a family with members with both severe and mild degree of thrombasthenia. Acta Paediatr Scand 56(2):189-197.
76. Stormorken H, Gogstad GO, Solum NO, Pande H (1982) Diagnosis of heterozygotes in Glanzmann's thrombasthenia. Thromb Haemost 48(2):217-221.
77. Levin J (2013) The evolution of mammalian platelets. Platelets, ed Michelson AD (Academic, London), 3rd Ed, pp 3-26.
78. Schmaier AA, et al. (2011) Occlusive thrombi arise in mammals but not birds in response to arterial injury: Evolutionary insight into human cardiovascular disease. Blood 118(13):3661-3669.
79. Veltman JA, Brunner HG (2012) De novo mutations in human genetic disease. Nat Rev Genet 13(8):565-575.
80. Duquesnoy RJ (2012) The antibody response to an HLA mismatch: A model for non-self-self discrimination in relation to HLA epitope immunogenicity. Int J Immunogenet 39(1):1-9.
81. Carrasco Pro S, Zimic M, Nielsen M (2014) Improved pan-specific MHC class I peptide-binding predictions using a novel representation of the MHC-binding cleft environment. Tissue Antigens 83(2):94-100.
82. Kaplan CNH, Freedman J (2013) Alloimmune thrombocytopenia. Platelets, ed Michelson AD (Academic, London), 3rd Ed, pp 953-970.
83. Abecasis GR, et al.; 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491(7422):56-65.
84. Fu W, et al.; NHLBI Exome Sequencing Project (2013) Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493(7431):216-220.
85. Lau TL, Kim C, Ginsberg MH, Ulmer TS (2009) The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J 28(9):1351-1361.
86. Yang J, et al. (2009) Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation. Proc Natl Acad Sci USA 106(42):17729-17734.
87. Metcalf DG, et al. (2010) NMR analysis of the alphaIIb beta3 cytoplasmic interaction suggests a mechanism for integrin regulation. Proc Natl Acad Sci USA 107(52):22481-22486.
88. Wang C, Bradley P, Baker D (2007) Protein-protein docking with backbone flexibility. J Mol Biol 373(2):503-519.
89. Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8(3):275-282.
90. Robin X, et al. (2011) pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12:77.