科研之友
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摘要
Conotoxins (CTxs) selectively target a range of ion channels and receptors, making them widely used tools for probing nervous system function. Conotoxins have been previously grouped into superfamilies according to signal sequence and into families based on their cysteine framework and biological target. Here we describe the cloning and characterization of a new conotoxin, from Conus vexillum, named alpha B-conotoxin VxXXIVA. The peptide does not belong to any previously described conotoxin superfamily and its arrangement of Cys residues is unique among conopeptides. Moreover, in contrast to previously characterized conopeptide toxins, which are expressed initially as prepropeptide precursors with a signal sequence, a "pro'' region, and the toxin-encoding region, the precursor sequence of alpha B-VxXXIVA lacks a "pro'' region. The predicted 40-residue mature peptide, which contains four Cys, was synthesized in each of the three possible disulfide arrangements. Investigation of the mechanism of action of alpha B-VxXXIVA revealed that the peptide is a nicotinic acetylcholine receptor (nAChR) antagonist with greatest potency against the alpha 9 alpha 10 subtype. H-1 nuclear magnetic resonance (NMR) spectra indicated that all three alpha B-VxXXIVA isomers were poorly structured in aqueous solution. This was consistent with circular dichroism (CD) results which showed that the peptides were unstructured in buffer, but adopted partially helical conformations in aqueous trifluoroethanol (TFE) solution. The alpha 9 alpha 10 nAChR is an important target for the development of analgesics and cancer chemotherapeutics, and alpha B-VxXXIVA represents a novel ligand with which to probe the structure and function of this protein.
- 出版日期2013-1-30
- 单位海南大学
