title: A naturally-occurring carboxyl-terminally truncated α-scorpion toxin is a blocker of sodium channels.
abstract: α-Scorpion toxins constitute a multigene family of evolutionarily conserved venom peptides that inhibit sodium channel inactivation and increase its peak current. Here, we describe the characterization of a new α-scorpion toxin gene expressed in the venom gland of Mesobuthus eupeus that encodes a carboxyl-terminally truncated product of 38 residues (named MeuNaTxα(NT)-1). Synthetic MeuNaTxα(NT)-1 was oxidized to form two disulfide bridges in an alkaline environment and the refolded peptide exhibits different structure and function from the classical α-scorpion toxin. MeuNaTxα(NT)-1 blocks sodium channels on rat dorsal root ganglia (DRG) neurons without impact on the inactivation of the channels. This work provides a clue for evolution-guided design of channel blockers for therapeutic aims.
authors.affiliation: Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Limei
authors.initials: L
authors.lastname: Zhu
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019020:Directed Molecular Evolution; D015195:Drug Design; D005088:Exocrine Glands / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012605:Scorpions / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012604:Scorpion Venoms; D026941:Sodium Channel Blockers