title: Defining the role of the tension sensor in the mechanosensitive channel of small conductance.
abstract: Mutations that alter the phenotypic behavior of the Escherichia coli mechanosensitive channel of small conductance (MscS) have been identified; however, most of these residues play critical roles in the transition between the closed and open states of the channel and are not directly involved in lipid interactions that transduce the tension response. In this study, we use molecular dynamic simulations to predict critical lipid interacting residues in the closed state of MscS. The physiological role of these residues was then investigated by performing osmotic downshock assays on MscS mutants where the lipid interacting residues were mutated to alanine. These experiments identified seven residues in the first and second transmembrane helices as lipid-sensing residues. The majority of these residues are hydrophobic amino acids located near the extracellular interface of the membrane. All of these residues interact strongly with the lipid bilayer in the closed state of MscS, but do not face the bilayer directly in structures associated with the open and desensitized states of the channel. Thus, the position of these residues relative to the lipid membrane appears related to the ability of the channel to sense tension in its different physiological states.
authors.affiliation: Department of Chemistry, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Malcolm
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Heo
authors.forename: Donald E
authors.initials: DE
authors.lastname: Elmore
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Maurer
mesh_terms: D000409:Alanine / Q000235:genetics; D001696:Biomechanical Phenomena; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D050356:Lipid Metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation / Q000235:genetics; D009995:Osmosis; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; C469542:MscS protein, E coli; D000409:Alanine