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Acta Biochimica et Biophysica Sinica

Year: 2009  |  Volume: 41  |  Issue: 10  |  Page No.: 858 - 864

Characterization of a novel {alpha}4/4-conotoxin, Qc1.2, from vermivorous Conus quercinus

C Peng, W Chen, Y Han, T Sanders, G Chew, J Liu, E Hawrot, C Chi and C. Wang

Abstract

As part of continuing studies of the identification of gene organization and cloning of novel -conotoxins, the first 4/4-conotoxin identified in a vermivorous Conus species, designated Qc1.2, was originally obtained by cDNA and genomic DNA cloning from Conus quercinus collected in the South China Sea. The predicted mature toxin of Qc1.2 contains 14 amino acid residues with two disulfide bonds (I-III, II-IV connectivity) in a native globular configuration. The mature peptide of Qc1.2 is supposed to contain an N-terminal post-translationally processed pyroglutamate residue and a free carboxyl C-terminus. This peptide was chemically synthesized and refolded for further characterization of its functional properties. The synthetic Qc1.2 has two interconvertible conformations in aqueous solution, which may be due to the cis-trans isomerization of the two successive Pro residues in its first Cys loop. Using the Xenopus oocyte heterologous expression system, Qc1.2 was shown to selectively inhibit both rat neuronal 3β2 and 3β4 subtypes of nicotinic acetylcholine receptors with low potency. A block of ~63% and 37% of the ACh-evoked currents was observed, respectively, and the toxin dissociated rapidly from the receptors. Compared with other characterized -conotoxin members, the unusual structural features in Qc1.2 that confer to its receptor recognition profile are addressed.

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