Structure of the Mechanosensitive Channel MscS Embedded in the Membrane Bilayer

• Published in: Journal of molecular biology 2019-08, Vol.431 (17), p.3081-3090
• Main Authors: Rasmussen, Tim, Flegler, Vanessa J., Rasmussen, Akiko, Böttcher, Bettina
• Format: Article
• Language: English
• Subjects: bacterial channel; cryo-electron microscopy; force-from-lipid principle; lipid–protein interaction; nanodiscs
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2019.07.006

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. •MscS, a mechanosensitive channel, opens in response to high tension in the membrane•The first structure of MscS within the membrane was obtained by cryo-EM to 2.9 Å•The paddles of MscS are only partly embedded in the membrane•21 lipid molecules are resolved within the complex, some coordinated by R59 and R88•Tension sensing relies on these molecular interactions of MscS with lipids [Display omitted]