TY - JOUR TI - Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS AU - Reddy, Bharat AU - Bavi, Navid AU - Lu, Allen AU - Park, Yeonwoo AU - Perozo, Eduardo A2 - Faraldo-Gómez, José D A2 - Aldrich, Richard W A2 - MacKinnon, Roderick A2 - Sukharev, Sergei VL - 8 PY - 2019 DA - 2019/12/27 SP - e50486 C1 - eLife 2019;8:e50486 DO - 10.7554/eLife.50486 UR - https://doi.org/10.7554/eLife.50486 AB - Prokaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND). They reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements. Two types of lipid densities are explicitly observed. A phospholipid that ‘hooks’ the top of each TM2-TM3 hairpin and likely plays a role in force sensing, and a bundle of acyl chains occluding the permeation path above the L105 cuff. These observations reshape our understanding of force-from-lipids gating in MscS and highlight the key role of allosteric interactions between TM segments and phospholipids bound to key dynamic components of the channel. KW - mechanotransduction KW - force-from-lipid gating KW - MscS KW - Cryo-EM JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -