Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake α-neurotoxins and nicotinic receptors
Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake α-neurotoxins and nicotinic receptors
复制标题
DOI：
10.1038/sj.emboj.7600620
复制
发表时间：
2005-04-20
期刊：
影响因子：
11.4
通讯作者：
Marchot, P
中科院分区：
文献类型：
--
作者：
Bourne, Y;Talley, TT;Marchot, P
蛇长α-神经毒素，α-眼镜蛇毒素，绑定到五聚体乙酰胆碱结合蛋白（AChBP）从滞水龙的晶体结构，解决了高质量的密度图，尽管4.2埃的整体分辨率。该结构明确地揭示了插入AChBP亚基界面的所有五个三指毒素分子的位置和方向以及与毒素结合相关的构象变化。AChBP环C和F边界的配体结合口袋移动显着从原来的位置，以包裹周围的尖端的毒素的第一和第二个手指和它的C-末端的一部分，而重排也发生在毒素的手指。在复杂的接口，主要的相互作用涉及芳香族和脂肪族侧链内的AChBP结合口袋，并在掩埋的尖端的毒素第二指，保守的苯丙氨酸和精氨酸残基，部分模仿绑定的激动剂分子。因此，这种结构，在揭示一个独特的和不可预测的构象的毒素结合乙酰胆碱BP分子，提供了一个铅模板类似的静息态构象的烟碱受体和理解的选择性curaremic α-神经毒素的各种受体物种。
The crystal structure of the snake long alpha-neurotoxin, alpha-cobratoxin, bound to the pentameric acetylcholine-binding protein ( AChBP) from Lymnaea stagnalis, was solved from good quality density maps despite a 4.2 angstrom overall resolution. The structure unambiguously reveals the positions and orientations of all five three-fingered toxin molecules inserted at the AChBP subunit interfaces and the conformational changes associated with toxin binding. AChBP loops C and F that border the ligand-binding pocket move markedly from their original positions to wrap around the tips of the toxin first and second fingers and part of its C-terminus, while rearrangements also occur in the toxin fingers. At the interface of the complex, major interactions involve aromatic and aliphatic side chains within the AChBP binding pocket and, at the buried tip of the toxin second finger, conserved Phe and Arg residues that partially mimic a bound agonist molecule. Hence this structure, in revealing a distinctive and unpredicted conformation of the toxin-bound AChBP molecule, provides a lead template resembling a resting state conformation of the nicotinic receptor and for understanding selectivity of curaremimetic alpha-neurotoxins for the various receptor species.