LAUSR

Snake venoms are potent cocktails containing a diverse array of proteins that typically target neuromuscular junctions or the hemostatic system of the snake’s prey. Many of the venom proteins that target hemostasis adopt a C-type lectinlike fold and are therefore termed snaclecs (ie, snake venom C-type lectins). Despite the structural similarity to functional lectins, the snaclecs do not exhibit carbohydrateor calciumbinding properties. Instead, the typical calcium-stabilized carbohydrate-binding loop found in functional lectins adopts a highly extended loop that forms a domain swap between α and β subunits in the snaclecs, forming an αβ heterodimer that interacts with critical proteins that control hemostasis. The resulting effect can be proor anticoagulant (eg, snaclecs that target factor IX, factor X, prothrombin, or α-thrombin) or proor antithrombotic (eg, snaclecs that target platelet receptors, such as glycoprotein Ibα, glycoprotein Ia/IIa, or GPVI [glycoprotein VI]). The structures of several snaclecs have been determined, revealing conserved features of the fold: each forms a disulfide-linked heterodimeric subunit of α and β chains that may comprise the mature protein (eg, factor X–binding protein or EMS16) or may further assemble into higher order structures, such as the (αβ) 4 rings of convulxin or flavocetin. Several structures have been reported for complexes between snaclecs and their targets, revealing that a concave surface between the α and β subunits interacts with the target protein to form an extensive binding site.