title: Investigating lipid composition effects on the mechanosensitive channel of large conductance (MscL) using molecular dynamics simulations.
abstract: Previous experimental work has shown that the functional properties of the mechanosensitive channel of large conductance (MscL) are affected by variations in lipid composition. Here, we utilize molecular dynamics simulations of Mycobacterium tuberculosis MscL to investigate such lipid composition effects on a molecular level. In particular, two sets of simulations were performed. In the first, trajectories using lipids with different headgroups (phosphatidylcholine and phosphatidylethanolamine) were compared. Protein-lipid interactions were clearly altered by the headgroup changes, leading to conformational differences in the C-terminal region of M. tuberculosis MscL. In the second set of simulations, lipid tails were gradually shortened, thinning the membrane over a molecular dynamics trajectory. These simulations showed evidence of hydrophobic matching between MscL and the lipid membrane, as previously proposed. For all simulations, protein-lipid interaction energies in the second transmembrane region were correlated to mutagenic data, emphasizing the importance of lipid interactions for proper MscL function.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Elmore
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Dougherty
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D016296:Mutagenesis; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D013997:Time Factors
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D008055:Lipids; C086596:MscL protein, E coli; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011506:Proteins; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine