SOLUTION STRUCTURE OF CARDIOTOXIN-V FROM NAJA-NAJA-ATRA

Cardiotoxins are small proteins that are found in the venoms of snakes from the Elapidae family. These toxins are known to bind to and disru pt the organization, integrity, and function of the cell membrane. Mos t of the well-studied cardiotoxins cause depolarization of membrane po tentials and/or lysis of red cells. In contrast, CTX V from Naja naja atra displays poor hemolytic activity but is proficient at inducing ag gregation and fusion of sphingomyelin vesicles [Chien et al. (1991) J. Biol. Chem. 266, 3252-3259]. To determine whether the unique activity of this CTX is attributable to its tertiary structure, the solution s tructure of CTX V was determined by NMR methods. On the basis of these studies, this cardiotoxin has the same general topology as other memb ers of the family, and thus its unusual properties do not arise from a ny gross structural differences that are detectable by solution NMR me thods. Molecular dynamics calculations indicate that residues 36-50 sh ow concerted fluctuations. On the basis of sequence similarity, we pos tulate that residues 30-34 are important in determining the specificit y of cardiotoxins for fusion versus lysis of vesicles.