Open AccessTwo Potent α3/5 Conotoxins from Piscivorous Conus achatinus
Author(s) -
LIU Li,
CHEW Geoffrey,
HAWROT Edward,
CHI Chengwu,
WANG Chunguang
Publication year - 2007
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2007.00301.x
Subject(s) - conotoxin , conus , nicotinic acetylcholine receptor , nicotinic antagonist , nicotinic agonist , acetylcholine receptor , biology , protein subunit , amino acid , receptor , biochemistry , chemistry , microbiology and biotechnology , anatomy , gene , peptide
Every cone snail produces a mixture of different conotoxins and secretes them to immobilize their prey and predators. α3/5 conotoxins, isolated from fish‐hunting cone snails, target muscle nicotinic acetylcholine receptors. The structure and function of α3/5 conotoxin from the piscivorous Conus achatinus have not been studied. We synthesized two pentadecamer peptides, Ac1. 1a and Ac1. 1b, with appropriate disulfide bonding, based on cDNA sequences of α3/5 conotoxins from C. achatinus. Ac1.1a and Ac1.1b differ by only one amino acid residue. They have similar potency on blocking recombinant mouse muscle acetylcholine receptor expressed in Xenopus laevis oocytes, with IC 50 values of 36 nM and 26 nM, respectively. For Ac1.1b, deletion of the first three N‐terminal amino acids did not change its activity, indicating that the N‐terminus is not involved in the interaction with its receptor. Furthermore, our experiments indicate that both toxins strongly prefer the α 1 δ subunit interface instead of the α 1 ‐γ binding site on the mouse muscle nicotinic acetylcholine receptor. These peptides provide additional tools for the study of the structure and function of nicotinic receptor.