Solution structure and backbone dynamics of an omega-conotoxin precursor

Nuclear magnetic resonance spectroscopy was used to characterize the soluti on structure and backbone dynamics of a putative precursor form of omega -c onotoxin MVIIA, a 25-amino-acid residue peptide antagonist of voltage-gated Ca2+ channels. The mature peptide is found in the venom of a fish-hunting marine snail Conus magus and contains an amidated carboxyl terminus that is generated by oxidative cleavage of a Gly residue. The form examined in thi s study is identical to the mature peptide except for the presence of the u nmodified carboxy-terminal Gly. This form, referred to as omega -MVIIA-Gly, has previously been shown to refold and form its disulfides more efficient ly than the mature form, suggesting that the presence of the terminal Gly m ay favor folding in vivo. The nuclear magnetic resonance (NMR) structure de termination indicated that the fold of omega -MVIIA-Gly is very similar to that previously determined for the mature form, but revealed that the termi nal Gly residue participates in a network of hydrogen bonds involving both backbone and side chain atoms, very likely accounting for the enhanced stab ility and folding efficiency. N-15 relaxation experiments indicated that th e backbone is well ordered on the nanosecond time scale but that residues 9 -15 undergo a conformational exchange processes with a time constant of sim ilar to 35 microseconds. Other studies have implicated this segment in the binding of the peptide to its physiological target, and the observed motion s may play a role in allowing the peptide to enter the binding site.