Diversity of Cobra Cardiotoxin

Abstract

Cardiotoxins (CTXs), the major component of cobra venom with three-finger loop structure similar to neurotoxins and muscarinic toxins, are cytolytic to many cells. Recent efforts in ellucidating the structure and function relationship of CTXs have resulted in the identification of several subgroups within the CTX family previously classified on the basis of primary sequence homology. The amino acid residues located at the tips of loop 1 and 3 are hydrophobic, making CTX membrane-active amphiphilic polypeptides which can be conveniently assayed by their unique sphingomyelin vesicles aggregation/fusion activity. There is significant variation in the amino acids near the tip of loop 2. Based on the presence of specific residues, P-type (with Pro-31) and S-type (with Ser-29) CTX exhibit strong and weak membrane binding activity, respectively. Distinct subgroup can further be classified within each CTX group based on the property of amino acid residue at position 33. For instance, Lys-33 containing P-type CTX binds stronger to heparin than Met-33 containing CTX, with dissociation constant differing by several orders of magnitude. Thus, the difficulty in the structure and function correlation of CTXs can be attributed, at least partially, to the diverse groups of CTX. In this article, functional roles of several specific residues of CTXs are reviewed to shed light on the action mechanism of CTXs on cell membranes. A clear understanding of the functional role of these specific residues would allow the design of high-affinity heparin binding polypeptides and a study of the interaction of β-sheet polypeptide with membrane phospholipids and receptors.