Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
IUBMB Life. 2011 Jun;63(6):375-82. doi: 10.1002/iub.461.
Aggregation of platelets is an essential step in the formation of a stable blood clot during vascular injury. The trypsin-like protease thrombin acts as the dominant agonist of platelet activation on engagement of protease-activated receptors (PARs). Important details on the molecular aspects of thrombin-PAR interactions have been revealed recently by structural biology. In the case of human platelets, PAR1 engages thrombin via an extended surface of recognition encompassing the active site and exosite I. In the case of murine platelets, PAR4 binds to the active site in a conformation that leaves exosite I free for interaction with cofactors like PAR3. Human PAR4 mimics the murine receptor binding mechanism for residues upstream of the scissile bond. This information is consistent with existing functional data and provides a solid background for future structural and mutagenesis studies of PAR interaction with thrombin and related proteases.
血小板聚集是血管损伤时形成稳定血栓的必要步骤。胰蛋白酶样蛋白酶凝血酶作为蛋白酶激活受体 (PARs) 激活血小板的主要激动剂。结构生物学最近揭示了凝血酶-PAR 相互作用的分子方面的重要细节。在人血小板的情况下，PAR1 通过包含活性位点和外位 I 的扩展识别表面与凝血酶结合。在鼠血小板的情况下，PAR4 结合到活性位点，其构象使外位 I 保持自由与 PAR3 等辅助因子相互作用。人 PAR4 模拟了对切割键上游残基的小鼠受体结合机制。这些信息与现有功能数据一致，并为 PAR 与凝血酶和相关蛋白酶相互作用的未来结构和突变研究提供了坚实的基础。
