Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward.
Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward.
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映射电压门控离子通道中的机电耦合途径：挑战和前进的道路。
DOI：
10.1016/j.jmb.2021.167104
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发表时间：
2021-08-20
影响因子：
5.6
通讯作者：
Chanda B
中科院分区：
文献类型：
--
作者：
Cowgill J;Chanda B
分子间和分子内的变构相互作用是多种生物大分子活性调节的基础。在电压门控离子通道超家族中，电压敏感结构域的构象状态通过这种长程变构相互作用调节孔结构域的活性。虽然这些通道的整体结构是保守的，但电压传感器和孔之间的变构相互作用在这个超家族的成员之间变化很大。尽管在确定介导机电耦合的关键残基和结构界面方面取得了进展，但我们对生物物理机制的理解仍然有限。电压门控离子通道在各种构象状态下的新结构将提供一个更好的三维视图的过程，但最终建立一个机制，我们还需要量化的各种结构元素对这个过程的能量贡献。使用严格的无偏指标，我们希望比较各个子家族之间的机电耦合效率，以便获得全面的了解。此外，对该过程的定量理解将使我们能够正确地参数化计算方法，这将最终使我们能够从结构中预测变构激活机制。在这篇综述中，我们将概述各种实验方法来测量机电耦合的挑战和局限性，并强调该领域的最佳实践。
Inter- and intra-molecular allosteric interactions underpin regulation of activity in a variety of biological macromolecules. In the voltage-gated ion channel superfamily, the conformational state of the voltage-sensing domain regulates the activity of the pore domain via such long-range allosteric interactions. Although the overall structure of these channels is conserved, allosteric interactions between voltage-sensor and pore varies quite dramatically between the members of this superfamily. Despite the progress in identifying key residues and structural interfaces involved in mediating electromechanical coupling, our understanding of the biophysical mechanisms remains limited. Emerging new structures of voltage-gated ion channels in various conformational states will provide a better three-dimensional view of the process but to conclusively establish a mechanism, we will also need to quantitate the energetic contribution of various structural elements to this process. Using rigorous unbiased metrics, we want to compare the efficiency of electromechanical coupling between various sub-families in order to gain a comprehensive understanding. Furthermore, quantitative understanding of the process will enable us to correctly parameterize computational approaches which will ultimately enable us to predict allosteric activation mechanisms from structures. In this review, we will outline the challenges and limitations of various experimental approaches to measure electromechanical coupling and highlight the best practices in the field.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1085/jgp.201210840
发表时间：
2012-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Chowdhury S;Chanda B
通讯作者：
Chanda B
DOI：
10.1074/jbc.m110.214650
发表时间：
2011-04-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Flynn GE;Zagotta WN
通讯作者：
Zagotta WN
影响因子：
4.8
作者：
Abderemane-Ali, Fayal;Es-Salah-Lamoureux, Zeineb;Loussouarn, Gildas
通讯作者：
Loussouarn, Gildas