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首页> 外文期刊>Journal of Molecular Biology >Interaction of the Mechanosensitive Channel, MscS, with the Membrane Bilayer through Lipid Intercalation into Grooves and Pockets
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Interaction of the Mechanosensitive Channel, MscS, with the Membrane Bilayer through Lipid Intercalation into Grooves and Pockets

机译：机械敏感通道，MSCs的相互作用，通过脂质插入到凹槽和口袋中的膜双层

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摘要

All membrane proteins have dynamic and intimate relationships with the lipids of the bilayer that may determine their activity. Mechanosensitive channels sense tension through their interaction with the lipids of the membrane. We have proposed a mechanism for the bacterial channel of small conductance, MscS, that envisages variable occupancy of pockets in the channel by lipid chains. Here, we analyze protein-lipid interactions for MscS by quenching of tryptophan fluorescence with brominated lipids. By this strategy, we define the limits of the bilayer for TM1, which is the most lipid exposed helix of this protein. In addition, we show that residues deep in the pockets, created by the oligomeric assembly, interact with lipid chains. On the cytoplasmic side, lipids penetrate as far as the pore-lining helices and lipid molecules can align along TM3b perpendicular to lipids in the bilayer. Cardiolipin, free fatty acids, and branched lipids can access the pockets where the latter have a distinct effect on function. Cholesterol is excluded from the pockets. We demonstrate that introduction of hydrophilic residues into TM3b severely impairs channel function and that even "conservative" hydrophobic substitutions can modulate the stability of the open pore. The data provide important insights into the interactions between phospholipids and MscS and are discussed in the light of recent developments in the study of Piezo1 and TrpV4. (C) 2019 The Authors. Published by Elsevier Ltd.
机译：所有膜蛋白质都具有动态和亲密的关系，与双层的脂质可以确定它们的活动。机械敏感通道通过与膜的脂质的相互作用感染张力。我们提出了一种用于小型电导，MSC的细菌通道的机制，其设想通过脂质链中的沟槽中的袋的可变占用。在此，我们通过用溴化脂质淬火色氨酸荧光来分析MSCs的蛋白质 - 脂质相互作用。通过这种策略，我们定义了TM1的双层的极限，这是该蛋白质的最脂质暴露的螺旋。此外，我们表明，由低聚组件产生的口袋深处的残留物与脂质链相互作用。在细胞质侧，只要孔隙螺旋螺旋和脂质分子可以沿着双层的脂质垂直于脂质的TM3B对准，脂质渗透。心脂，游离脂肪酸和支链脂质可以进入后者对功能具有明显影响的口袋。胆固醇被排除在口袋之外。我们证明将亲水残留物引入TM3B严重危害通道功能，甚至“保守”疏水取代可以调节开放孔的稳定性。数据提供了对磷脂和MSC之间的相互作用的重要见解，并且根据Piezo1和Trpv4研究的最新发展讨论。 （c）2019年作者。 elsevier有限公司出版

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