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摘要 : 2015年9月23日,自然出版集团综合性学术期刊《Scientific Reports 》上在线发表了同济大学生命科学学院王春光课题组的题为“Conotoxin αD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors”的研究论文。

 2015年9月23日,自然出版集团综合性学术期刊《Scientific Reports 》上在线发表了同济大学生命科学学院王春光课题组的题为“Conotoxin αD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors”的研究论文。论文由王春光课题组与中科院上海生科院的丁建平教授课题组和澳大利亚RMIT大学David J. Adams教授课题组合作完成,同济大学生命科学学院2010级博士生徐少琼为本文的第一作者。




Conotoxin αD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors


Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting αD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of αD-GeXXA, GeXXA-CTD, retains inhibitory activity against the α9α10 nAChR subtype. Furthermore, we identified that His7 of the rat α10 nAChR subunit determines the species preference of αD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that αD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of αD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds.

来源: Scientific Reports 浏览次数:0


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