Channelpedia

PubMed 15677695


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.2 , Nav1.5



Title: Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1.

Authors: Li-Hui Liu, Frank Bosmans, Chantal Maertens, Ron-Han Zhu, Da-Cheng Wang, Jan Tytgat

Journal, date & volume: FASEB J., 2005 Apr , 19, 594-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15677695


Abstract
In-depth structure-function studies of voltage-gated Na+ channels and peptide toxins are continuously increasing our understanding of their interaction. In this study, an effective yeast expression system was used to study the role of 14 N- and C-terminal residues from the alpha-like toxin BmK M1 from the Chinese scorpion Buthus martensii Karsch. With the use of site-directed mutagenesis, all of these residues were individually substituted by one or more amino acids, resulting in a total of 19 mutants. These were then subjected to a bioassay on mice, an elaborate electrophysiological characterization on three cloned voltage-gated Na+ channels (Nav1.2, Nav1.5, and para), and a circular dichroism analysis. Our results reveal large mutant-dependent differences that emphasize important and specific roles for the studied residues. By mutating single amino acids, we were able to redirect the alpha-like characteristics of BmK M1 (active on both mammals and insects) to either much higher mammal specificity or, in a few cases, total insect specificity. This study therefore represents a thorough mapping and elucidation of three epitopes that underlie the molecular basis of the mammalian and insecticidal potency of the scorpion alpha-like toxin, BmK M1 on voltage-gated Na+ channels.