A new conotoxin affecting sodium current inactivation interacts with the delta-conotoxin receptor site.
We describe a new peptide conotoxin affecting sodium current inactivation, that competes on binding with delta-conotoxin TxVIA (delta 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 delta TxVIA but differs in its net charge. NgVIA competes with delta TxVIA on binding to rat brain synaptosomes and molluscan central nervous system and strongly inhibits sodium current inactivation in snail neurons, as does delta TxVIA. In contrast to delta 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. delta 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 delta TxVIA but similar to that of Conus striatus toxin. This new toxin provides a lead for structure-function relationship studies in the delta-conotoxins and will enable analysis of the functional significance of this complex of receptor sites in gating mechanisms of sodium channels.
Fainzilber
M
M
Department of Cell and Animal Biology, Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
Lodder
J C
JC
Kits
K S
KS
Kofman
O
O
Vinnitsky
I
I
Van Rietschoten
J
J
Zlotkin
E
E
Gordon
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D020916:Conotoxins; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers
D020916:Conotoxins; D010455:Peptides; D017981:Receptors, Neurotransmitter; D026941:Sodium Channel Blockers; C091655:conotoxin NgVIA; D012964:Sodium