title: E. coli outer membrane and interactions with OmpLA.
abstract: The outer membrane of Gram-negative bacteria is a unique asymmetric lipid bilayer composed of phospholipids (PLs) in the inner leaflet and lipopolysaccharides (LPSs) in the outer leaflet. Its function as a selective barrier is crucial for the survival of bacteria in many distinct environments, and it also renders Gram-negative bacteria more resistant to antibiotics than their Gram-positive counterparts. Here, we report the structural properties of a model of the Escherichia coli outer membrane and its interaction with outer membrane phospholipase A (OmpLA) utilizing molecular dynamics simulations. Our results reveal that given the lipid composition used here, the hydrophobic thickness of the outer membrane is ∼3 Å thinner than the corresponding PL bilayer, mainly because of the thinner LPS leaflet. Further thinning in the vicinity of OmpLA is observed due to hydrophobic matching. The particular shape of the OmpLA barrel induces various interactions between LPS and PL leaflets, resulting in asymmetric thinning around the protein. The interaction between OmpLA extracellular loops and LPS (headgroups and core oligosaccharides) stabilizes the loop conformation with reduced dynamics, which leads to secondary structure variation and loop displacement compared to that in a DLPC bilayer. In addition, we demonstrate that the LPS/PL ratios in asymmetric bilayers can be reliably estimated by the per-lipid surface area of each lipid type, and there is no statistical difference in the overall membrane structure for the outer membranes with one more or less LPS in the outer leaflet, although individual lipid properties vary slightly.
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas.
authors.forename: Emilia L
authors.initials: EL
authors.lastname: Wu
authors.affiliation: T. C. Jenkins Department of Biophysics, John Hopkins University, Baltimore, Maryland.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Fleming
authors.affiliation: Korean Institute of Science and Technology Information, Daejeon, Korea.
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Yeom
authors.affiliation: Department of Organic Chemistry and Stockholm Center for Biomembrane Research, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Widmalm
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Maryland, College Park, Maryland.
authors.forename: Jeffery B
authors.initials: JB
authors.lastname: Klauda
authors.affiliation: T. C. Jenkins Department of Biophysics, John Hopkins University, Baltimore, Maryland. Electronic address: Karen.Fleming@jhu.edu.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Fleming
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas. Electronic address: wonpil@ku.edu.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D054466:Phospholipases A1 / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D054466:Phospholipases A1; C412876:outer membrane phospholipase A