α-RgIA:: A novel conotoxin that specifically and potently blocks the α9α10 nAChR
α-RgIA:: A novel conotoxin that specifically and potently blocks the α9α10 nAChR
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DOI：
10.1021/bi0520129
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发表时间：
2006-02-07
期刊：
影响因子：
2.9
通讯作者：
Olivera, BM
中科院分区：
文献类型：
--
作者：
Ellison, M;Haberlandt, C;Olivera, BM
α 9和α 10烟碱乙酰胆碱受体（nAChR）亚基组装形成α 9 α 10 nAChR亚型。该受体被认为介导传出橄榄耳蜗纤维和耳蜗毛细胞之间的胆碱能突触传递。此外，在背根神经节神经元、淋巴细胞、皮肤角质形成细胞和垂体结节部中已经描述了α 9和/或α 10表达。选择性阻断α 9 α 10通道的特异性拮抗剂可能是阐明其在这些不同组织中作用的有价值的工具。本研究描述了来自西大西洋物种大王芋螺的新型α-芋螺毒素，α-芋螺毒素RgIA（α-RgIA），其是α 9 α 10 nAChR的亚型特异性阻断剂。α-RgIA属于α-芋螺毒素家族的α 4/3亚家族; α-RgIA和先前表征的α 4/3毒素之间的序列和亚型特异性比较表明α-RgIA的C-末端一半中的氨基酸负责其对α 9 α 10 nAChR亚型的优先抑制。
The alpha 9 and alpha 10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha 9 alpha 10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha 9 and/or alpha 10 expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, and the pars tuberalis of the pituitary. Specific antagonists that selectively block the alpha 9 alpha 10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific blocker of the alpha 9 alpha 10 nAChR. alpha-RgIA belongs to the alpha 4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha 4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha 9 alpha 10 nAChR subtype.