title: The role of lipids in mechanosensation.
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.
authors.affiliation: Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
authors.forename: Christos
authors.initials: C
authors.lastname: Pliotas
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: A Caroline E
authors.initials: AC
authors.lastname: Dahl
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Rasmussen
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, UK.
authors.forename: Kozhinjampara R
authors.initials: KR
authors.lastname: Mahendran
authors.affiliation: Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Smith
authors.affiliation: Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
authors.forename: Phedra
authors.initials: P
authors.lastname: Marius
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gault
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Thandiwe
authors.initials: T
authors.lastname: Banda
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Akiko
authors.initials: A
authors.lastname: Rasmussen
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Miller
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, UK.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, UK.
authors.forename: Hagan
authors.initials: H
authors.lastname: Bayley
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.|Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Booth
authors.affiliation: Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.|State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
authors.forename: James H
authors.initials: JH
authors.lastname: Naismith
mesh_terms: D055592:Biophysical Phenomena; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D007473:Ion Channels / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; C469542:MscS protein, E coli; D010743:Phospholipids