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Title: Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1
Authors: Liu, LH ×
Bosmans, Frank
Tytgat, Jan
Maertens, Chantal
Zhu, Ron-Han
Wang, Da-Cheng #
Issue Date: Apr-2005
Publisher: Federation amer soc exp biol
Series Title: FASEB Journal vol:19 issue:6 pages:594-6
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 a-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 (Na(v)1.2, Na(v)1.5, 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 a-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 a-like toxin, BmK M1 on voltage-gated Na+ channels.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
× corresponding author
# (joint) last author

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