Structural and dynamic characterization of omega-conotoxin MVIIA: The binding loop exhibits slow conformational exchange

omega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from t he venom of the sea snail Conus magus that binds to neuronal N-type calcium channels. Tt forms a compact folded structure, presenting a loop between C ys8 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 fle xible, Broadening of a subset of resonances in the NMR spectrum at low temp erature, anomalous temperature dependence of the chemical shifts of some re sonances, and exchange contributions to J(0) from C-13 relaxation measureme nts reveal that conformational exchange affects the residues in this loop. The effects of this exchange on the calculated structure of tu-conotoxin MV IIA are discussed. The exchange appears to be associated with a change in t he conformation of the disulfide bridge Cys8-Cys20, The implications for th e use of the omega-conotoxins as a scaffold for carrying other functions is discussed.