Forces and energetics of the canonical tetrameric cation channel gating.
Forces and energetics of the canonical tetrameric cation channel gating.
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规范四聚体阳离子通道门控的力和能量学。
DOI：
10.1073/pnas.2221616120
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发表时间：
2023-07-11
影响因子：
11.1
通讯作者：
Scheuring, Simon
中科院分区：
文献类型：
--
作者：
Scheuring, Simon
所有四聚体阳离子通道共享具有特征性螺旋-孔-环-螺旋结构的相同孔域。典型的阳离子通道功能涉及通过孔环的离子选择性和通过孔衬螺旋的运动的门控。然而，对门控过程的物理学知之甚少。在这里，我利用MthK结构和熵聚合物拉伸物理模型来推导通道门控中涉及的力和能量。在MthK中，仅门控环中的构象变化就通过未折叠的连接子将通道打开，从而提供了使用物理模型计算门控中涉及的力（9.8 pN（皮牛顿））和能量（3.6kBT）的独特机会。四聚体阳离子通道的规范门控机制涉及在所谓的交叉门处的孔衬螺旋的扩展。尽管有丰富的结构信息，我们缺乏门控过程的物理描述。在这里，我利用了熵聚合物拉伸物理模型和MthK结构，推导出涉及孔域门控的力和能量。在MthK中，仅RCK结构域中的Ca 2+诱导的构象变化通过经由未折叠的连接体的拉动打开了竞争交叉门。在开放构象中，连接体充当RCK结构域和交叉门之间的熵弹簧，其存储3.6kBT的弹性势能并施加9.8pN（皮牛顿）径向拉力以保持门打开。我进一步推导出，加载连接子以准备打开通道的功高达3.8kBT，施加高达15.5 pN以拉开通道。打开十字交叉导致3.3kBT弹簧势能的释放。因此，封闭的/RCK-apo和开放的/RCK-Ca 2+构象被几个kBT的屏障分开。我讨论了这些发现如何与MthK的功能特性，并建议，鉴于所有四聚体阳离子通道之间的螺旋孔环螺旋孔域的建筑保护，这些物理参数可能是相当普遍的。
All tetrameric cation channels share the same pore domain with the characteristic helix–pore-loop–helix architecture. Canonical cation channel function involves ion selectivity by the pore loops and gating by movements of the pore-lining helices. However, much less is known about the physics of the gating process. Here, I took advantage of MthK structures and an entropic polymer stretching physics model to derive the forces and energies involved in channel gating. In MthK, conformational changes in the gating ring alone pull the channel open via unfolded linkers, offering the unique opportunity to use a physical model to calculate the forces, 9.8 pN (piconewton), and energies, 3.6kBT, involved in gating. The canonical gating mechanism of tetrameric cation channels involves the spreading of the pore-lining helices at the so-called bundle-crossing gate. Despite a wealth of structural information, we lack a physical description of the gating process. Here, I took advantage of an entropic polymer stretching physical model and MthK structures to derive the forces and energies involved in pore-domain gating. In MthK, the Ca2+-induced conformational change in the RCK domain alone opens the bundle-crossing gate through pulling via unfolded linkers. In the open conformation, the linkers serve as entropic springs between the RCK domain and bundle-crossing gate that store an elastic potential energy of 3.6kBT and exert 9.8 pN (piconewton) radial pulling force to keep the gate open. I further derive that the work to load the linkers to prime the channel for opening is up to 3.8kBT, exerting up to 15.5 pN to pull the bundle-crossing open. Opening of the bundle-crossing leads to a release of 3.3kBT spring potential energy. Thus, the closed/RCK-apo and the open/RCK-Ca2+ conformations are separated by a barrier of several kBT. I discuss how these findings relate to the functional properties of MthK and suggest that given the architectural conservation of the helix–pore-loop–helix pore-domain among all tetrameric cation channels, these physical parameters might be quite general.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
4.3
作者：
Girodat D;Pati AK;Terry DS;Blanchard SC;Sanbonmatsu KY
通讯作者：
Sanbonmatsu KY
DOI：
10.1085/jgp.200609655
发表时间：
2007-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Li Y;Berke I;Chen L;Jiang Y
通讯作者：
Jiang Y
影响因子：
4.8
作者：
Parfenova, Lyubov V.;Crane, Brittany M.;Rothberg, Brad S.
通讯作者：
Rothberg, Brad S.
影响因子：
16.8
作者：
Posson, David J.;McCoy, Jason G.;Nimigean, Crina M.
通讯作者：
Nimigean, Crina M.