Mechanosensitive channel YnaI has lipid-bound extended sensor paddles.

Mechanosensitive channel YnaI has lipid-bound extended sensor paddles.
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机械敏感通道 YnaI 具有脂质结合的扩展传感器板。

DOI:
10.1038/s42003-021-02122-0
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发表时间:
2021-05-20
影响因子:
5.9
通讯作者:
Zheng H
Zheng H
中科院分区:
生物学2区
文献类型:
--
作者:
Hu W;Wang Z;Zheng H

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细菌机械敏感通道(MS)的一般机制已经通过对大肠杆菌(E. coli)的小电导通道MscS的广泛研究来表征。然而,最近对同一通道的结构研究表明,各种通道结合脂类在通道门控中的作用存在争议。为了更好地理解细菌的MscS样通道,有必要对MscS以外的同源物进行表征。在这里,我们描述了YnaI的结构,它是大肠杆菌中最接近的MscS同源物之一,在3.3 Å分辨率下通过冷冻电子显微镜测定其非导电状态。我们的结构揭示了YnaI中完整的膜传感器桨结构域,该结构域由重要的功能残基H43、Q46、Y50和K93稳定。在传感器桨片之间的口袋中,有明显的脂质密度与残基Q100和R120强烈相互作用。这些脂质是天然脂质的混合物,但可能富含心磷脂和磷脂酰丝氨酸。此外,还讨论了沿离子传导途径和负责七聚体组装的残基。结合生化实验和诱变研究,我们的研究结果有力地支持了口袋脂质在机械敏感通道中具有重要功能的观点。Hu, Wang和Zheng描述了封闭状态下细菌mscs样通道YnaI的低温电镜结构。他们进一步描述了其附着在MscS n端的扩展桨结构域、桨之间的脂质袋、离子传导途径和七聚体组装,最后讨论了其机械传感机制。
The general mechanism of bacterial mechanosensitive channels (MS) has been characterized by extensive studies on a small conductance channel MscS from Escherichia coli (E. coli). However, recent structural studies on the same channel have revealed controversial roles of various channel-bound lipids in channel gating. To better understand bacterial MscS-like channels, it is necessary to characterize homologs other than MscS. Here, we describe the structure of YnaI, one of the closest MscS homologs in E. coli, in its non-conducting state at 3.3 Å resolution determined by cryo electron microscopy. Our structure revealed the intact membrane sensor paddle domain in YnaI, which was stabilized by functionally important residues H43, Q46, Y50 and K93. In the pockets between sensor paddles, there were clear lipid densities that interact strongly with residues Q100 and R120. These lipids were a mixture of natural lipids but may be enriched in cardiolipin and phosphatidylserine. In addition, residues along the ion-conducting pathway and responsible for the heptameric assembly were discussed. Together with biochemical experiments and mutagenesis studies, our results provide strong support for the idea that the pocket lipids are functionally important for mechanosensitive channels. Hu, Wang & Zheng describe the cryo-EM structure of a bacterial MscS-like channel, named YnaI, in closed state. They further describe its extended paddle domain that is attached to the N-terminus of MscS, lipid pockets between paddles, its ion-conducting pathway, and its heptameric assembly, finally discussing its mechanosensing mechanism.
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