Mechanosensitive channel gating by delipidation
Autor: | Kristin Hellmanzik, Vanessa Schmidt, Vanessa Judith Flegler, Jessica Löffler, Tim Rasmussen, Bettina Böttcher, Akiko Rasmussen, Julia Halang, Karina Borbil, Lea Boten, Hsuan-Ai Chen, Cihan Makbul, Rainer Hedrich, Christian Kraft, Hanna Deinlein |
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Rok vydání: | 2021 |
Předmět: |
Models
Molecular Multidisciplinary Protein Conformation Chemistry Cell Membrane Conductance Gating Periplasmic space Biological Sciences Lipid Metabolism Lipids Mechanotransduction Cellular Micelle Cytosol Transmembrane domain Membrane Osmotic Pressure Catalytic Domain Biophysics Mechanosensitive channels Ion Channel Gating |
Zdroj: | Proc Natl Acad Sci U S A |
ISSN: | 1091-6490 0027-8424 |
Popis: | 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 Å 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-β-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. |
Databáze: | OpenAIRE |
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