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The role of lipids in mechanosensation

DOI: 10.1038/nsmb.3120 DOI Help

Authors: Christos Pliotas (University of St Andrews) , A Caroline E. Dahl (University of Oxford) , Tim Rasmussen (University of Aberdeen) , Kozhinjampara R Mahendran (University of Oxford) , Terry K Smith (University of St. Andrews) , Phedra Marius (University of St. Andrews) , Joseph Gault (University of Oxford) , Thandiwe Banda (University of Aberdeen) , Akiko Rasmussen (University of Aberdeen) , Samantha Miller (University of Aberdeen) , Carol V. Robinson (University of Oxford) , Hagan Bayley (University of Oxford) , Mark S. P. Sansom (University of Oxford) , Ian R. Booth (University of Aberdeen) , James H Naismith (Center for Biomolecular Sciences, University of St. Andrews)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 22 , PAGES 991 - 998

State: Published (Approved)
Published: November 2015

Abstract: The ability of proteins to sense membrane tension is pervasive in biology. A higher-resolution structure of the Escherichia coli small-conductance mechanosensitive channel MscS identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids, and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (with two acyl chains) from MscS pockets and trigger channel opening. We propose that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS. When interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable, and the channel gates.

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography