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Structural basis of thrombin–protease‐activated receptor interactions
Author(s) -
Gandhi Prafull S.,
Chen Zhiwei,
Appelbaum Eric,
Zapata Fatima,
Di Cera Enrico
Publication year - 2011
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.461
Subject(s) - thrombin , scissile bond , protease activated receptor , proteases , protease , chemistry , biochemistry , receptor , trypsin , thrombin receptor , active site , microbiology and biotechnology , platelet , biophysics , biology , enzyme , immunology
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. © 2011 IUBMB IUBMB Life, 63(6): 375–382, 2011