Ugarova T P, Budzynski A Z, Shattil S J, Ruggeri Z M, Ginsberg M H, Plow E F
Committee on Vascular Biology, Scripps Research Institute, La Jolla, California 92037.
J Biol Chem. 1993 Oct 5;268(28):21080-7.
The binding of fibrinogen to membrane glycoprotein GPIIb-IIIa on activated platelets leads to platelet aggregation. This interaction results in conformational changes in fibrinogen as evidenced by the expression of receptor-induced binding sites, RIBS, epitopes which are expressed by the bound but not the free ligand. In the present study, two RIBS epitopes have been localized. One sequence resides at gamma 112-119 and is recognized by mAb 9F9; the second is the RGDF sequence at A alpha 95-98 and is recognized by mAb 155B16. These epitopes are also exposed by adsorption of fibrinogen onto a plastic surface and digestion of the molecule by plasmin. Proteolytic exposure of the epitopes coincides with cleavage of the carboxyl-terminal aspects of the A alpha-chains to form fragment X2. The inaccessibility of the RGDF sequence at A alpha 95-98 in fibrinogen suggests that this sequence does not participate in the initial binding of the molecule to GPIIb-IIIa. The location of these RIBS epitopes suggests a model in which binding of fibrinogen to its receptor alters the conformation of the carboxyl-terminal aspects of the A alpha-chains, exposing the sequences which reside in the coiled-coil connector segments between the D and E domains of the molecule. These sequences may then serve as epitopes and may mediate unique functions of the receptor-bound molecule.
纤维蛋白原与活化血小板上的膜糖蛋白GPIIb-IIIa结合会导致血小板聚集。这种相互作用会导致纤维蛋白原发生构象变化，这可通过受体诱导结合位点（RIBS）表位的表达得到证明，这些表位由结合态而非游离配体表达。在本研究中，已确定了两个RIBS表位。一个序列位于γ链112 - 119位，可被单克隆抗体9F9识别；第二个是Aα链95 - 98位的RGDF序列，可被单克隆抗体155B16识别。这些表位也可通过纤维蛋白原吸附到塑料表面以及纤溶酶对该分子的消化作用而暴露出来。表位的蛋白水解暴露与Aα链羧基末端形成片段X2的裂解过程一致。纤维蛋白原中Aα链95 - 98位的RGDF序列难以接近，这表明该序列不参与分子与GPIIb-IIIa的初始结合。这些RIBS表位的位置提示了一种模型，即纤维蛋白原与其受体的结合会改变Aα链羧基末端的构象，暴露出位于分子D和E结构域之间的卷曲螺旋连接段中的序列。这些序列随后可能作为表位，并可能介导受体结合分子的独特功能。
