Structural and Dynamic Characterization of ω-Conotoxin MVIIA:  The Binding Loop Exhibits Slow Conformational Exchange^†,‡

ω-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from the venom of the sea snail Conus magus that binds to neuronal N-type calcium channels. It forms a compact folded structure, presenting a loop between Cys8 and Cys15 that contains a set of residues critical for its binding. The loop does not have a unique defined structure, nor is it intrinsically flexible. Broadening of a subset of resonances in the NMR spectrum at low temperature, anomalous temperature dependence of the chemical shifts of some resonances, and exchange contributions to J(0) from ¹³C relaxation measurements reveal that conformational exchange affects the residues in this loop. The effects of this exchange on the calculated structure of ω-conotoxin MVIIA are discussed. The exchange appears to be associated with a change in the conformation of the disulfide bridge Cys8-Cys20. The implications for the use of the ω-conotoxins as a scaffold for carrying other functions is discussed.