EVIDENCE FOR NOVEL BINDING-SITES ON THE PLATELET GLYCOPROTEIN IIB AND IIIA SUBUNITS AND IMMOBILIZED FIBRINOGEN

被引:21
|
作者
PARISE, LV
STEINER, B
NANNIZZI, L
CRISS, AB
PHILLIPS, DR
机构
[1] UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,CARDIOVASC RES INST,SAN FRANCISCO,CA 94141
[2] UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94141
[3] UNIV N CAROLINA,SCH MED,CTR THROMBOSIS & HEMOSTASIS,CHAPEL HILL,NC 27599
基金
美国国家卫生研究院;
关键词
D O I
10.1042/bj2890445
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
The present study was designed to examine the interaction of the purified platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa or integrin alpha(IIb)beta3) and the individual subunits of the complex with immobilized fibrinogen. Although I-125-GP IIb-IIIa binding to fibrinogen immobilized on Sepharose was specific, this inter-action exhibited properties distinct from those of reversible fibrinogen binding to platelets: I-125-GP IIb-IIIa binding appeared irreversible, but non-covalent, Ca2+-independent, and was inhibited only weakly, or not at all, by the anti-(GP IIb-IIIa) monoclonal antibodies 10E5 and 7E3 and synthetic peptides from known platelet-binding domains of fibrinogen. Reversibly dissociated GP IIb or GP IIIa subunits inhibited I-125-GP IIb-IIIa binding to immobilized fibrinogen and bound directly to the fibrinogen. However, these subunits did not bind to peptides derived from known platelet-binding domains within the fibrinogen alpha- and gamma-chains, although the GP IIb-IIIa complex did. These results show that the complexed form of full-length GP IIb and GP IIIa is required for binding to these synthetic peptides, but not necessarily for binding to immobilized fibrinogen. Thus GP IIb-IIIa can bind to immobilized fibrinogen by a distinct mechanism that appears to involve novel binding sites on each subunit of the GP IIb-IIIa complex and on fibrinogen.
引用
收藏
页码:445 / 451
页数:7
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