Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom.
Crotamine is a component of the venom of the snake Crotalus durissus terrificus and it belongs to the myotoxin protein family. It is a 42 amino acid toxin cross-linked by three disulfide bridges and characterized by a mild toxicity (LD50 = 820 micro g per 25 g body weight, i.p. injection) when compared to other members of the same family. Nonetheless, it possesses a wide spectrum of biological functions. In fact, besides being able to specifically modify voltage-sensitive Na+ channel, it has been suggested to exhibit analgesic activity and to be myonecrotic. Here we report its solution structure determined by proton NMR spectroscopy. The secondary structure comprises a short N-terminal alpha-helix and a small antiparallel triple-stranded beta-sheet arranged in an alphabeta1beta2beta3 topology never found among toxins active on ion channels. Interestingly, some scorpion toxins characterized by a biological activity on Na+ channels similar to the one reported for crotamine, exhibit an alpha/beta fold, though with a beta1alphabeta2beta3 topology. In addition, as the antibacterial beta-defensins, crotamine interacts with lipid membranes. A comparison of crotamine with human beta-defensins shows a similar fold and a comparable net positive potential surface. To the best of our knowledge, this is the first report on the structure of a toxin from snake venom active on Na+ channel.
Nicastro
Giuseppe
G
Department of Experimental Medicine, Section of Chemistry and Structural Biochemistry, University of Parma, Italy.
Franzoni
Lorella
L
de Chiara
Cesira
C
Mancin
Adriana C
AC
Giglio
Josè R
JR
Spisni
Alberto
A
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003435:Crotalid Venoms / Q000737:chemistry* / Q000378:metabolism; D017839:Crotalus / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry; D016415:Sequence Alignment; D015222:Sodium Channels / Q000378:metabolism*; D023083:beta-Defensins / Q000737:chemistry
D003435:Crotalid Venoms; D012604:Scorpion Venoms; D015222:Sodium Channels; D023083:beta-Defensins; C010563:crotamine