Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels.
Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels.
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KirBac1.1 突变体的分子动力学模拟揭示了 Kir 通道的全局门控变化。
DOI：
10.1021/acs.jcim.5b00010
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发表时间：
2015-04-27
影响因子：
5.6
通讯作者：
Stary-Weinzinger, Anna
中科院分区：
文献类型：
--
作者：
Linder, Tobias;Wang, Shizhen;Zangerl-Plessl, Eva-Maria;Nichols, Colin G.;Stary-Weinzinger, Anna
原核生物的内向整流钾通道(KirBac)与哺乳动物的KIR通道同源。它们的活性受动态构象变化的控制，这些构象变化调节着离子通过中心孔的流动。要了解KIR通道在门控过程中的动态重排，需要从不同构象结晶的通道中获得高分辨率的结构信息，并深入了解转变步骤，这是很难通过实验获得的。在这项研究中，我们使用MD模拟野生型KirBa1.1和一个激活突变体来研究KirBac通道的激活门控。全原子MD模拟显示，在143位引入谷氨酸会导致螺旋束跨越闸门的显著加宽，从而使水通量进入空腔。此外，在细胞质结构域中观察到了包括扭转运动在内的全局重排以及亚基界面的局部重排。这些结构重排与最近报道的封闭和开放构象的KirBac3.1晶体结构相似，表明我们的模拟捕捉到了KirBac1.1开放过程中的主要构象变化。此外，观察到蛋白质-脂质相互作用在门控过程中的重要作用。在激活门控过程中，滑动螺旋和C连接子与脂质的相互作用增强。
Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insight into the transition steps, which are difficult to access experimentally. In this study, we use MD simulations on wild type KirBac1.1 and an activatory mutant to investigate activation gating of KirBac channels. Full atomistic MD simulations revealed that introducing glutamate in position 143 causes significant widening at the helix bundle crossing gate, enabling water flux into the cavity. Further, global rearrangements including a twisting motion as well as local rearrangements at the subunit interface in the cytoplasmic domain were observed. These structural rearrangements are similar to recently reported KirBac3.1 crystal structures in closed and open conformation, suggesting that our simulations capture major conformational changes during KirBac1.1 opening. In addition, an important role of protein–lipid interactions during gating was observed. Slide-helix and C-linker interactions with lipids were strengthened during activation gating.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1074/jbc.c400417200
发表时间：
2004-11-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Enkvetchakul D;Bhattacharyya J;Jeliazkova I;Groesbeck DK;Cukras CA;Nichols CG
通讯作者：
Nichols CG