A New Conotoxin Affecting Sodium Current Inactivation Interacts with the -Conotoxin Receptor Site

• Published in: The Journal of biological chemistry Vol. 270; no. 3; p. 1123
• Main Authors: Michael Fainzilber, Johannes C. Lodder, Karel S. Kits, Ora Kofman, Ilya Vinnitsky, Jurphaas Van Rietschoten, Eliahu Zlotkin, Dalia Gordon
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 20-01-1995
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.3.1123

We describe a new peptide conotoxin affecting sodium current inactivation, that competes on binding with -conotoxin TxVIA ( TxVIA). The amino acid sequence of the new toxin, designated conotoxin NgVIA (NgVIA), is SKCFSOGTFCGIKOGLCCSVRCFSLFCISFE (where
O is trans -4-hydroxyproline). The primary structure of NgVIA has an identical cysteine framework and similar hydrophobicity as TxVIA but differs in its net charge. NgVIA competes with TxVIA on binding to rat brain synaptosomes and molluscan central nervous system and strongly inhibits sodium current inactivation
in snail neurons, as does TxVIA. In contrast to TxVIA, NgVIA is a potent paralytic toxin in vertebrate systems, its binding appears to be voltage-dependent, and it synergically
increases veratridine-induced sodium influx to rat brain synaptosomes. TxVIA acts as a partial antagonist to NgVIA in rat brain in vivo . NgVIA appears to act via a receptor site distinct from that of TxVIA but similar to that of Conus striatus toxin. This new toxin provides a lead for structure-function relationship studies in the -conotoxins and will enable analysis of the functional significance of this complex of receptor sites in gating mechanisms
of sodium channels.