Vol41 No.10: 858-864

Characterization of a novel alpha4/4-conotoxin, Qc1.2, from vermivorous Conus quercinus

Can Peng¹, Weihua Chen¹, Yuhong Han², Tanya Sanders³, Geoffrey Chew³, Jing Liu³, Edward Hawrot³, Chengwu Chi^1,2*, and Chunguang Wang^1*

(1 Institute of Protein Research, Tongji University, Shanghai 200092, China; 2 Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 3 Department of Molecular Pharmacology, Physiology and Biotechnology, Brown Medical School, Providence, RI 02912, USA)

Abstract
����As part of continuing studies of the identification of gene organization and cloning of novel alpha-conotoxins, the first alpha4/4-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 alpha3beta2 and alpha3beta4 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 alpha-conotoxin members, the unusual structural features in Qc1.2 that confer to its receptor recognition profile are addressed.

Received: 2009-5-16����Accepted: 2009-6-26

*Corresponding author . Tel: +86-21-65984347; Fax: +86-21-65988403; E-mail: [email protected] (C.W.); Tel: +86-21-54921165; Fax: +86 21-54921011; E-mail: [email protected] (C.C.)

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