Biocenter and Rudolf Virchow Center, Universität Würzburg, Haus D15, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
Biocenter and Rudolf Virchow Center, Universität Würzburg, Haus D15, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
J Mol Biol. 2019 Aug 9;431(17):3081-3090. doi: 10.1016/j.jmb.2019.07.006. Epub 2019 Jul 7.
Since life has emerged, gradients of osmolytes over the cell membrane cause pressure changes in the cell and require tight regulation to prevent cell rupture. The mechanosensitive channel of small conductance (MscS) releases solutes and water when a hypo-osmotic shock raises the pressure in the cell. It is a member of a large family of MscS-like channels found in bacteria, archaea, fungi and plants and model for mechanosensation. MscS senses the increase of tension in the membrane directly by the force from the lipids, but the molecular mechanism is still elusive. We determined the lipid interactions of MscS by resolving the structure of Escherichia coli MscS embedded in membrane discs to 2.9-Å resolution using cryo-electron microscopy. The membrane is attached only to parts of the sensor paddles of MscS, but phospholipid molecules move through grooves into remote pockets on the cytosolic side. On the periplasmic side, a lipid bound by R88 at the pore entrance is separated from the membrane by TM1 helices. The N-terminus interacts with the periplasmic membrane surface. We demonstrate that the unique membrane domain of MscS promotes deep penetration of lipid molecules and shows multimodal interaction with the membrane to fine-tune tension sensing.
自从生命出现以来，细胞膜上渗透物的浓度梯度会导致细胞内的压力变化，需要进行严格的调节以防止细胞破裂。当渗透休克导致细胞内压力升高时，小电导机械敏感通道（MscS）会释放溶质和水。它是细菌、古菌、真菌和植物中发现的一大类 MscS 样通道的成员，也是机械敏感性的模型。MscS 通过脂质的力直接感知膜张力的增加，但分子机制仍不清楚。我们通过使用冷冻电子显微镜将大肠杆菌 MscS 嵌入膜盘的结构解析到 2.9-Å 分辨率，确定了 MscS 的脂质相互作用。膜仅附着在 MscS 的传感器桨叶的部分上，但磷脂分子通过沟槽移动到胞质侧的远程口袋中。在周质侧，位于孔入口处的 R88 结合的脂质与 TM1 螺旋分离。N 端与周质膜表面相互作用。我们证明，MscS 的独特膜域促进了脂质分子的深入渗透，并显示出与膜的多种相互作用，以微调张力感应。
