title: Spontaneous formation of detergent micelles around the outer membrane protein OmpX.
abstract: The structure and flexibility of the outer membrane protein X (OmpX) in a water-detergent solution and in pure water are investigated by molecular dynamics simulations on the 100-ns timescale and compared with NMR data. The simulations allow for an unbiased determination of the structure of detergent micelles and the protein-detergent mixed micelle. The short-chain lipid dihexanoylphosphatidylcholine, as a detergent, aggregates into pure micelles of approximately 18 molecules, or alternatively, it binds to the protein surface. The detergent binds in the form of a monolayer ring around the hydrophobic beta-barrel of OmpX rather than in a micellar-like oblate; approximately 40 dihexanoylphosphatidylcholine lipids are sufficient for an effective suppression of water from the surface of the beta-barrel region. The phospholipids bind also on the extracellular, protruding beta-sheet. Here, polar interactions between charged amino acids and phosphatidylcholine headgroups act as condensation seed for detergent micelle formation. The polar protein surface remains accessible to water molecules. In total, approximately 90-100 detergent molecules associate within the protein-detergent mixed micelle, in agreement with experimental estimates. The simulation results indicate that OmpX is not a water pore and support the proposed role of the protruding beta-sheet as a "fishing rod".
authors.affiliation: Department of Biochemistry, University of Zürich, Zürich, Switzerland. rainer.boeckmann@bioinf.uni-sb.de
authors.forename: Rainer A
authors.initials: RA
authors.lastname: Böckmann
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D003198:Computer Simulation; D003902:Detergents / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology*; D006867:Hydrolases / Q000737:chemistry* / Q000502:physiology*; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D015233:Models, Statistical; D010713:Phosphatidylcholines / Q000737:chemistry; D010742:Phospholipid Ethers / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: C052298:1,2-dihexadecyl-sn-glycero-3-phosphocholine; D001425:Bacterial Outer Membrane Proteins; D003902:Detergents; D029968:Escherichia coli Proteins; D008055:Lipids; D008823:Micelles; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D011506:Proteins; D012997:Solvents; D014867:Water; C482905:OmpX protein, E coli; C032166:1,2-hexanoylphosphatidylcholine; D006867:Hydrolases