Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Thromb Haemost. 2010 Nov;104(5):894-902. doi: 10.1160/TH10-09-0578. Epub 2010 Oct 12.
The main question concerning the mechanism of a-thrombin binding to platelet membrane glycoprotein (GP)Ib is whether it involves both thrombin exosite I and exosite II. The solution of two independent crystal structures suggests alternative explanations that may actually reflect different modes of binding with distinct pathophysiological significance. With respect to function, it is still unclear whether thrombin binding to GPIb promotes procoagulant and prothrombotic pathways of response to vascular injury or limits such responses by sequestering, at least temporarily, the active enzyme. We review here published information on these topics and touch upon ongoing studies aimed at finding definitive answers to outstanding questions relevant for a better understanding of thrombosis and haemostasis.
关于 a-凝血酶与血小板膜糖蛋白 (GP)Ib 结合机制的主要问题是,它是否涉及凝血酶外切酶 I 和外切酶 II。两个独立晶体结构的解决方案提出了替代解释,这些解释实际上可能反映了不同的结合模式,具有不同的病理生理意义。就功能而言,目前尚不清楚凝血酶与 GPIb 的结合是促进血管损伤后的促凝和促血栓形成反应,还是通过至少暂时隔离活性酶来限制这种反应。在这里,我们回顾了这些主题的已发表信息,并探讨了正在进行的研究,旨在为理解血栓形成和止血的相关问题提供明确答案。