Structure and sodium channel activity of an excitatory I 1-superfamily conotoxin

Abstract

Conotoxin ι-RXIA, from the fish-hunting species Conus radiatus, is a member of the recently characterized I1-superfamily, which contains eight cysteine residues arranged in a -C-C-CC-CC-C-C- pattern. ι-RXIA (formerly designated r11a) is one of three characterized I1 peptides in which the third last residue is posttranslationally isomerized to the D configuration. Naturally occurring ι-RXIA with D-Phe44 is significantly more active as an excitotoxin than the L-Phe analogue both in vitro and in vivo. We have determined the solution structures of both forms by NMR spectroscopy, the first for an I1-superfamily member. The disulfide connectivities were determined from structure calculations and c..