Snake venom modulators of platelet adhesion receptors and their ligands
Snake venom modulators of platelet adhesion receptors and their ligands
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DOI：
10.1016/s0041-0101(99)00187-7
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发表时间：
2000-06-01
期刊：
影响因子：
2.8
通讯作者：
Berndt, MC
中科院分区：
文献类型：
--
作者：
Andrews, RK;Berndt, MC
在血栓形成中，血小板聚集由特异性膜糖蛋白（GP）Ib-IX-V复合物与其粘附配体（血管性血友病因子）结合引发，该复合物位于破裂的动脉粥样硬化斑块基质中或暴露于高流体动力学剪切应力的血浆中。该过程与高剪切下的正常止血非常相似，其中GP Ib-IX-V依赖性血小板粘附至受损血管壁中的von Willebrand因子引发血小板活化和整合素α IIb β 3（GP IIb-IIIa）依赖性血小板聚集。在低剪切下，其它受体如结合胶原蛋白的受体、整合素α 2 β 1（GP Ia-IIa）或GP VI介导血小板粘附。最近，蛇毒蛋白已被鉴定为选择性调节血小板功能，通过靶向GP Ib-IX-V、α 2 β 1、GP VI、α IIb β 3或它们各自的配体促进或抑制血小板聚集。有趣的是，这些毒液蛋白通常属于两个主要蛋白质家族之一，C型凝集素家族或金属蛋白酶-去整合素。本文综述了蛇毒蛋白调节血小板功能的构效关系，以及这些新型探针以意想不到的方式为我们理解血栓形成的分子机制做出了贡献。(C)2000爱思唯尔科技有限公司版权所有。
In thrombosis, platelet aggregation is initiated by a specific membrane glycoprotein (GP) Ib-IX-V complex binding to its adhesive ligand, von Willebrand factor, in the matrix of ruptured atherosclerotic plaques or in plasma exposed to high hydrodynamic shear stress. This process closely resembles normal haemostasis at high shear, where GP Ib-IX-V-dependent platelet adhesion to von Willebrand factor in the injured blood vessel wall initiates platelet activation and integrin alpha IIb beta 3 (GP IIb-IIIa)-dependent platelet aggregation. At low shear, other receptors such as those that bind collagen, the integrin alpha 2 beta 1 (GP Ia-IIa) or GP VI, mediate platelet adhesion. Recently, snake venom proteins have been identified that selectively modulate platelet function, either promoting or inhibiting platelet aggregation by targeting GP Ib-IX-V, alpha 2 beta 1, GP VI, alpha IIb beta 3, or their respective ligands. Interestingly, these venom proteins typically belong to one of two major protein families, the C-type lectin family or the metalloproteinase-disintegrins. This review focuses on recent insights into structure-activity relationships of snake venom proteins that regulate platelet function, and the ways in which these novel probes have contributed in unexpected ways to our understanding of the molecular mechanisms underlying thrombosis. (C) 2000 Elsevier Science Ltd. All rights reserved.