Symbol Disintegrin InterPro IPR001762 SCOP 1kst | Pfam PF00200 PROSITE PDOC00351 SUPERFAMILY 1kst | |
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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.
Contents
Operation
Disintegrins work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors. Integrins 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.
Types of disintegrin
Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin, schistatin, echistatin, elegantin, eristicophin, flavoridin, halysin, kistrin, mojastin (Crotalus scutulatus), rubistatin (Crotalus ruber), tergeminin, salmosin and triflavin.
Disintegrins are split into 5 classes: small, medium, large, dimeric, and snake venom metalloproteinases.
Small Disintegrins: 49-51 amino acids, 4 disulfide bonds
Medium Disintegrins: 70 amino acids, 6 disulfide bonds
Large Disintegrins: 84 amino acids, 7 disulfide bonds
Dimeric Disintegrins: 67 amino acids, 4 intra-chain disulfide bonds
Snake Venom Metalloproteinases: 100 amino acids, 8 disulfide bond
Evolution of disintegrin family
Disintegrins evolved via gene duplication of an ancestral protein family, the ADAM family. Small, medium, large, and dimeric disintegrin family are found only in the Viperidae family, suggesting duplication and diversification about 12-20 million years ago. Snake venom metalloproteinases are found through the entire Colubroidea superfamily, suggesting that they evolved before Colubroidea diversified roughly 60 million years ago.