Multifunctional Snake C-Type Lectins Affecting Platelets

Abstract

Snake venoms contain a wide range of components, many of which affect haemostasis by activation or inhibition of platelets or coagulation factors. They can be classified into groups based on structure and mode of action. One group is the snake C-type lectins, so called because of the typical folding which closely resembles that found in classical C-type lectins, such as selectins and mannose-binding proteins. Unlike the classic C-type lectins, those from snakes are generally heterodimeric with two subunits, α and β. Some are multimeric heterodimers. The subunits have homologous sequences and are generally linked by a disulphide bond as well as by swapping loops. One of the first C-type lectins with a defined function was echicetin which was demonstrated to bind to platelet GPIb and block several functions of this receptor. Since then, many proteins with similar structure have been reported to act on platelet receptors or coagulation factors and several have been crystallized. These proteins were thought to be specific for a single platelet receptor or coagulation factor, i.e. they had only one receptor per heterodimer. Recent studies show that most of these C-type lectins have binding sites for more than one ligand and have complex mechanisms of action.

Protein complexes in snake venom

“…[135], hemagglutinating activities [136,137] and platelet aggregation [138,139]. They are homodimers of subunits containing 135-141-amino acid residues [140].…”

Exploring the proteomes of the venoms of the Peruvian pit vipers Bothrops atrox, B. barnetti and B. pictus

“…Venoms produced by snakes of the viperidae family, sub families crotalinae (pit vipers) and viperinae (true vipers) are complex mixtures of active molecules which show a diverse array of effects both on prey and human victims. In order to immobilize or kill the prey and also to assist in their digestion, snakes have evolved the ability to store more than a dozen proteins/toxins belonging to different protein families in a single venom gland [2]. Several studies indicated that the genus Bothrops is a paraphyletic group with respect to the forest pit vipers (Bothriopsis) and comprises 36 species commonly referred to as lanceheads, which are distributed throughout tropical and non-tropical Latin America [3][4][5][6].…”

The Collagen-binding Integrin α2β1 Is a Novel Interaction Partner of the Trimeresurus flavoviridis Venom Protein Flavocetin-A

“…CLRPs not only target integrin A domains but also other receptors such as the platelet receptor GPIb and blood coagulation factors (9). GPIb is a receptor for the plasma glycoprotein vWF, which initiates platelet adhesion to exposed vascular subendothelium, consequently activating platelets and leading to hemostasis (10,11).…”