The amino acid sequence of μ-conotoxin GIIIA (otherwise called geographutoxin I), a peptide having 22 amino acid residues with three disulfide bridges, was modified by replacing each residue with Ala or Lys to elucidate its active center for blocking sodium channels of skeletal muscle. NMR and CD spectra were virtually identical between native and modified toxins, indicating the similarity of their conformation including disulfide bridges. The inhibitory effect of these modified peptides on twitch contractions of the rat diaphragm showed that Arg at the 13th position and the basicity of the molecule are crucial for the biological action. The segment Lys11-Asp12-Arg13 has been reported to be flexible (Lancelin, J.-M., Kohda, D., Tate, S., Yanagawa, Y., Abe, T., Satake, M., and Inagaki, F. (1991) Biochemistry, in press), and this may represent a clue for the subtle fit of Arg13 to the specific site of sodium channels. Since known ligands to sodium channels, such as tetrodotoxin, anthopleulin-A, etc., contain guanidino groups as a putative binding moiety, Arg may be a general residue for peptide toxins to interact with the receptor site on sodium channels.
|Number of pages||3|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 1991|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology