Clemetson Kenneth J, Lu Qiumin, Clemetson Jeannine M
Theodor Kocher Institute, University of Berne, Berne, Switzerland.
Pathophysiol Haemost Thromb. 2005;34(4-5):150-5. doi: 10.1159/000092414.
Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with alpha and beta subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, alpha2beta1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin alpha2beta1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.
蛇毒是生物活性蛋白质和肽的复杂混合物。许多蛇毒通过激活或抑制凝血因子、血小板，或破坏内皮细胞来影响止血。蛇毒成分可分为不同家族，如丝氨酸蛋白酶、金属蛋白酶、C型凝集素样蛋白、去整合素和磷脂酶。蛇毒C型凝集素样蛋白具有典型的折叠结构，类似于选择素和甘露糖结合蛋白等经典C型凝集素。现在已经鉴定出许多蛇毒C型凝集素样蛋白，它们是由α和β亚基组成的异二聚体结构，常通过多聚化形成大分子。它们通过与血管性血友病因子（VWF）或特定受体如糖蛋白Ib（GPIb）、α2β1和糖蛋白VI（GPVI）结合来激活血小板。简单的异二聚体GPIb结合分子主要抑制血小板功能，而多聚体则激活血小板。一系列四聚体蛇毒C型凝集素样蛋白通过与GPVI结合来激活血小板，而另一系列则通过整合素α2β1影响血小板功能。有些通过诱导VWF与GPIb结合起作用。这些蛋白质的许多结构，通常与其配体复合，已经被确定。结构-活性研究表明，尽管这些蛋白质具有相似的主链折叠，但它们的作用机制相当复杂。蛇C型凝集素样蛋白通常与不止一种血小板受体相互作用，并且具有复杂的作用机制。
