Critical residues of integrin alpha IIb subunit for binding of alpha IIb beta 3 (glycoprotein IIb-IIIa) to fibrinogen and ligand-mimetic antibodies (PAC-1, OP-G2, and LJ-CP3)

被引:85
作者
Kamata, T
Irie, A
Tokuhira, M
Takada, Y
机构
[1] Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA
[2] KEIO UNIV, SCH MED, DEPT INTERNAL MED, SHINJUKU KU, TOKYO 160, JAPAN
关键词
D O I
10.1074/jbc.271.31.18610
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Integrin alpha IIb beta 3 plays a critical role in platelet aggregation through its interaction with fibrinogen, Elucidation of the mechanisms of alpha IIb beta 3-fibrinogen interaction is critical to understanding hemostasis and thrombosis. Here we report that mutations of Gly-184, Tyr-189, Tyr-190, Phe-191, and Gly-193 within the predicted turn structure of the third amino-terminal repeat of alpha IIb significantly block binding of alpha IIb beta 3 to soluble fibrinogen. These mutations also block binding of alpha IIb beta 3 to ligand-mimetic monoclonal antibodies PAC-1, OP-G2, LJ-CP3, which have an RGD-related RYD sequence in their antigen-binding sites, These mutations do not significantly affect the expression of alpha IIb beta 3, in contrast to most of the natural alpha IIb mutations occurring in Glanzmann's thrombasthenic patients, The data suggest that these residues are critically involved in alpha IIb beta 3-ligand interactions.
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页码:18610 / 18615
页数:6
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