A molecular framework for temperature-dependent gating of ion channels.
A molecular framework for temperature-dependent gating of ion channels.
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离子通道温度依赖性门控的分子框架。
DOI：
10.1016/j.cell.2014.07.026
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发表时间：
2014-08-28
期刊：
影响因子：
64.5
通讯作者：
Chanda B
中科院分区：
文献类型：
--
作者：
Chowdhury S;Jarecki BW;Chanda B
高等生物体对热或冷的感知是由专门的离子通道介导的，其门控对温度极其敏感。事实证明，这种温度敏感门控的物理化学基础很难解析。在这里，我们采用了自下而上的蛋白质设计方法，并合理设计了离子通道以响应热刺激而激活。通过改变溶剂化中经历状态依赖性变化的位点的氨基酸极性，我们能够系统地赋予规范电压门控离子通道温度敏感性。我们的结果表明，通道选通过程中的比热容变化是热敏选通的主要决定因素。我们还表明，门控电荷的减少放大了设计通道的温度敏感性，这解释了所有已知的温度门控离子通道中的低电压敏感性。这些新兴原理提出了一种看似合理的温度依赖性门控分子机制，它协调了具有整体保守跨膜结构的离子通道如何表现出广泛的温度传感表型。
Perception of heat or cold in higher organisms is mediated by specialized ion channels whose gating is exquisitely sensitive to temperature. The physicochemical underpinnings of this temperature-sensitive gating have proven difficult to parse. Here, we took a bottom-up protein design approach, and rationally engineered ion channels to activate in response to thermal stimuli. By varying amino acid polarities at sites undergoing state-dependent changes in solvation, we were able to systematically confer temperature-sensitivity to a canonical voltage-gated ion channel. Our results imply that the specific heat capacity change during channel gating is a major determinant of thermo-sensitive gating. We also show that reduction of gating charges amplifies temperature-sensitivity of designer channels which accounts for low voltage-sensitivity in all known temperature-gated ion channels. These emerging principles suggest a plausible molecular mechanism for temperature-dependent gating that reconcile how ion channels with an overall conserved transmembrane architecture may exhibit a wide range of temperature-sensing phenotypes.
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影响因子：
16.8
作者：
Li Q;Wanderling S;Paduch M;Medovoy D;Singharoy A;McGreevy R;Villalba-Galea CA;Hulse RE;Roux B;Schulten K;Kossiakoff A;Perozo E
通讯作者：
Perozo E
DOI：
10.1073/pnas.0406773101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Brauchi, S;Orio, P;Latorre, R
通讯作者：
Latorre, R
影响因子：
16.2
作者：
Larsson, HP;Baker, OS;Isacoff, EY
通讯作者：
Isacoff, EY
影响因子：
16.6
作者：
Chen, Jun;Kang, Dawon;Xu, Jing;Lake, Marc;Hogan, James O.;Sun, Chaohong;Walter, Karl;Yao, Betty;Kim, Donghee
通讯作者：
Kim, Donghee
影响因子：
4
作者：
Latorre, Ramon;Brauchi, Sebastian;Vargas, Guillermo
通讯作者：
Vargas, Guillermo