Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities

摘要

C-type lectin-like proteins (CLPs) have a variety of biological activities, including anticoagulant- and platelet-modulating activities but have no lectin activity. CLPs are made up of heterodimers or oligomers of heterodimers, while C-type lectins from snake venom are composed exclusively of homodimers or homooligomers. In the last decade, numerous CLPs, such as blood coagulation factor IX/X-binding protein and botrocetin, have been isolated from various snake venoms, sequenced, and characterized. In addition, RVV-X (factor X activator) and carinactivase-1 (prothrombin activator) are metalloproteases composed of two C-type lectin-like domains that recognize the Gla domain of factor X and prothrombin, respectively. The basic structures of these CLI's include two homologous subunits: subunit alpha (A chain) of 14-15 kDa and subunit beta (beta chain) of 13-14 kDa. CLPs occur in a variety of oligomeric forms, including 0, (0)2, and (alpha beta)(4). The basic homologous dimer (alpha beta) of these CLPs is formed by three-dimensional (3D) domain swapping. The CLPs constitute a new protein family and are useful tools for elucidating the mechanisms involved in clotting and platelet activation as well as the structure-function relationships of both blood clotting factors and platelet glycoproteins. (c) 2005 Elsevier Ltd. All rights reserved.