Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance
Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance
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DOI：
10.1038/s41467-020-17538-1
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发表时间：
2020-07-23
影响因子：
16.6
通讯作者：
Yuan, Peng
中科院分区：
文献类型：
--
作者：
Deng, Zengqin;Maksaev, Grigory;Yuan, Peng
机械敏感离子通道将物理力转化为电化学信号，这是一系列基本生理过程的基础，包括听觉、触觉、本体感觉、渗透调节和形态发生。小电导的机械敏感通道（MscS）构成了一个非常多样化的通道超家族，对渗透压的管理至关重要。在这里，我们展示了来自拟南芥MSL1的MscS同源物的低温电镜结构，可能是在封闭和开放状态下。七聚体MSL1通道包含一个不寻常的碗状跨膜区域，这让人联想到进化上和结构上无关的机械敏感压电通道。当通道打开时，MSL1的弯曲跨膜结构域变平并扩展。我们的结构，结合功能分析，描绘了机械敏感通道在膜张力增加下打开的结构机制。此外，不相关通道之间的共同结构特征表明，由非平面跨膜域引起的膜变形可能产生统一的机械门控机制。
Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive channels of small conductance (MscS) constitute a remarkably diverse superfamily of channels critical for management of osmotic pressure. Here, we present cryo-electron microscopy structures of a MscS homolog from Arabidopsis thaliana, MSL1, presumably in both the closed and open states. The heptameric MSL1 channel contains an unusual bowl-shaped transmembrane region, which is reminiscent of the evolutionarily and architecturally unrelated mechanosensitive Piezo channels. Upon channel opening, the curved transmembrane domain of MSL1 flattens and expands. Our structures, in combination with functional analyses, delineate a structural mechanism by which mechanosensitive channels open under increased membrane tension. Further, the shared structural feature between unrelated channels suggests the possibility of a unified mechanical gating mechanism stemming from membrane deformation induced by a non-planar transmembrane domain.