Insight into the modulation of Shaw2 Kv channels by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR.
Insight into the modulation of Shaw2 Kv channels by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR.
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深入了解全身麻醉药对 Shaw2 Kv 通道的调节：通过 NMR 对胶束中的 S4-S5 连接子和 S6 C 端肽进行结构和功能研究。
DOI：
10.1016/j.bbamem.2012.09.025
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Germann,MarkusW
中科院分区：
文献类型：
--
作者：
Zhang,Jin;Qu,Xiaoguang;Covarrubias,Manuel;Germann,MarkusW
The modulation of the Drosophila Shaw2 Kv channel by 1-alkanols and inhaled anesthetics is correlated with the involvement of the S4–S5 linker and C-terminus of S6, and consistent with stabilization of the channel's closed state. Structural analysis of peptides from S4–S5 (L45) and S6 (S6c), by nuclear magnetic resonance and circular dichroism spectroscopy supports that an α-helical conformation was adopted by L45, while S6c was only in an unstable/dynamic partially folded α-helix in dodecylphosphocholine micelles. Solvent accessibility and paramagnetic probing of L45 revealed that L45 lies parallel to the surface of micelles with charged and polar residues pointing towards the solution while hydrophobic residues are buried inside the micelles. Chemical shift perturbation introduced by 1-butanol on residues Gln320, Thr321, Phe322 and Arg323 of L45, as well as Thr423 and Gln424 of S6c indicates possible anesthetic binding sites on these two important components in the channel activation apparatus. Diffusion measurements confirmed the association of L45, S6c and 1-butanol with micelles which suggests the capability of 1-butanol to influence a possible interaction of L45 and S6c in the micelle environment.
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