%0 Journal Article %1 flegler2021mechanosensitive %A Flegler, V. J. %A Rasmussen, A. %A Borbil, K. %A Boten, L. %A Chen, H. A. %A Deinlein, H. %A Halang, J. %A Hellmanzik, K. %A Loffler, J. %A Schmidt, V. %A Makbul, C. %A Kraft, C. %A Hedrich, R. %A Rasmussen, T. %A Bottcher, B. %D 2021 %J Proc Natl Acad Sci U S A %K Catalytic Domain myOwn uni_network %N 33 %R 10.1073/pnas.2107095118 %T Mechanosensitive channel gating by delipidation %U https://www.ncbi.nlm.nih.gov/pubmed/34376558https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379960/pdf/pnas.202107095.pdf %V 118 %X The mechanosensitive channel of small conductance (MscS) protects bacteria against hypoosmotic shock. It can sense the tension in the surrounding membrane and releases solutes if the pressure in the cell is getting too high. The membrane contacts MscS at sensor paddles, but lipids also leave the membrane and move along grooves between the paddles to reside as far as 15 A away from the membrane in hydrophobic pockets. One sensing model suggests that a higher tension pulls lipids from the grooves back to the membrane, which triggers gating. However, it is still unclear to what degree this model accounts for sensing and what contribution the direct interaction of the membrane with the channel has. Here, we show that MscS opens when it is sufficiently delipidated by incubation with the detergent dodecyl-beta-maltoside or the branched detergent lauryl maltose neopentyl glycol. After addition of detergent-solubilized lipids, it closes again. These results support the model that lipid extrusion causes gating: Lipids are slowly removed from the grooves and pockets by the incubation with detergent, which triggers opening. Addition of lipids in micelles allows lipids to migrate back into the pockets, which closes the channel even in the absence of a membrane. Based on the distribution of the aliphatic chains in the open and closed conformation, we propose that during gating, lipids leave the complex on the cytosolic leaflet at the height of highest lateral tension, while on the periplasmic side, lipids flow into gaps, which open between transmembrane helices.

@article{flegler2021mechanosensitive, abstract = {The mechanosensitive channel of small conductance (MscS) protects bacteria against hypoosmotic shock. It can sense the tension in the surrounding membrane and releases solutes if the pressure in the cell is getting too high. The membrane contacts MscS at sensor paddles, but lipids also leave the membrane and move along grooves between the paddles to reside as far as 15 A away from the membrane in hydrophobic pockets. One sensing model suggests that a higher tension pulls lipids from the grooves back to the membrane, which triggers gating. However, it is still unclear to what degree this model accounts for sensing and what contribution the direct interaction of the membrane with the channel has. Here, we show that MscS opens when it is sufficiently delipidated by incubation with the detergent dodecyl-beta-maltoside or the branched detergent lauryl maltose neopentyl glycol. After addition of detergent-solubilized lipids, it closes again. These results support the model that lipid extrusion causes gating: Lipids are slowly removed from the grooves and pockets by the incubation with detergent, which triggers opening. Addition of lipids in micelles allows lipids to migrate back into the pockets, which closes the channel even in the absence of a membrane. Based on the distribution of the aliphatic chains in the open and closed conformation, we propose that during gating, lipids leave the complex on the cytosolic leaflet at the height of highest lateral tension, while on the periplasmic side, lipids flow into gaps, which open between transmembrane helices.}, added-at = {2024-02-15T15:11:54.000+0100}, author = {Flegler, V. J. and Rasmussen, A. and Borbil, K. and Boten, L. and Chen, H. A. and Deinlein, H. and Halang, J. and Hellmanzik, K. and Loffler, J. and Schmidt, V. and Makbul, C. and Kraft, C. and Hedrich, R. and Rasmussen, T. and Bottcher, B.}, biburl = {https://www.bibsonomy.org/bibtex/2a98bf9df7013a82dc42125a4fc0374f2/jvsi_all}, doi = {10.1073/pnas.2107095118}, interhash = {91dc3989bc4de25528a6f41d1fa9bbe3}, intrahash = {a98bf9df7013a82dc42125a4fc0374f2}, issn = {1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking)}, journal = {Proc Natl Acad Sci U S A}, keywords = {Catalytic Domain myOwn uni_network}, note = {Flegler, Vanessa Judith Rasmussen, Akiko Borbil, Karina Boten, Lea Chen, Hsuan-Ai Deinlein, Hanna Halang, Julia Hellmanzik, Kristin Loffler, Jessica Schmidt, Vanessa Makbul, Cihan Kraft, Christian Hedrich, Rainer Rasmussen, Tim Bottcher, Bettina eng Research Support, Non-U.S. Gov't 2021/08/12 Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):e2107095118. doi: 10.1073/pnas.2107095118.}, number = 33, timestamp = {2024-02-15T15:11:54.000+0100}, title = {Mechanosensitive channel gating by delipidation}, type = {Journal Article}, url = {https://www.ncbi.nlm.nih.gov/pubmed/34376558https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379960/pdf/pnas.202107095.pdf}, volume = 118, year = 2021 }