Structural Basis of Thrombin-Protease-Activated Receptor Interactions

被引：22

作者：

Gandhi, Prafull S. ^{[1
]}

Chen, Zhiwei ^{[1
]}

Appelbaum, Eric ^{[1
]}

Zapata, Fatima ^{[1
]}

Di Cera, Enrico ^{[1
]}

机构：

[1] St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA

来源：

IUBMB LIFE | 2011年 / 63卷 / 06期

基金：

美国国家卫生研究院;

关键词：

X-ray crystallography; platelet; protease-activated receptors; PLATELET ACTIVATION; CRYSTAL-STRUCTURE; ALPHA-THROMBIN; COMPLEX; THROMBOMODULIN; SPECIFICITY; BINDING; ENZYME; SITE; HEMOSTASIS;

D O I：

10.1002/iub.461

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：

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. (C) 2011 IUBMB IUBMB Life, 63(6): 375-382,2011

引用

页码：375 / 382

页数：8

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