Disintegrin

Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.

They work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors. Integrin are cell receptors involved in cell–cell and cell–extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet–platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor–glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen. The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant.

Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin, schistatin , echistatin , elegantin, eristicophin, flavoridin , halysin, kistrin, tergeminin, salmosin and triflavin.

Disintegrin-like proteins are found in various species ranging from slime mold to humans. Some other proteins known to contain a disintegrin domain are:


 * Some snake venom zinc metalloproteinases consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B), atrolysin-e (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post-translational processing.
 * The beta-subunit of guinea pig sperm surface protein PH30 . PH30 is a protein involved in sperm-egg fusion. The beta subunit contains a disintegrin at the N-terminal extremity.
 * Mammalian epididymial apical protein 1 (EAP I) . EAP I is associated with the sperm membrane and may play a role in sperm maturation. Structurally, EAP I consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.
 * ADAM and ADAMTS protein families, which include important protease enzymes. As an example, the secreted protease ADAMTS13, found in serum, cleaves Von Willebrand factor and acts as a natural, endogenous, inhibitor of platelet adhesion and aggregation.