title: Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore opening.
abstract: The molecular forces that drive structural transitions between the open and closed states of channels and transporters are not well understood. The gate of the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight into the channel-opening mechanism, we measured interaction energies between the relevant side chains by double-mutant cycle analysis and correlated these with the channel activities of corresponding point mutants. The closed central salt bridge has a strong interaction energy of -5.6 kcal mol(-1), which can be broken by forming the open-state salt bridge Glu52-Lys82 (DeltaDeltaG(Inter) = -3.5 kcal mol(-1)) and a weak interaction between Arg138 and Glu128 (DeltaDeltaG(Inter) = -0.6 kcal mol(-1)). A covalent disulfide bond in place of the central salt bridge completely blocks the channel. Growth assays indicate that this gating mechanism could physiologically contribute to the osmoprotection of Escherichia coli cells from environmental stress.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia Health System, PO Box 800736, Charlottesville, Virginia 22908-0736, USA.
authors.forename: Heedeok
authors.initials: H
authors.lastname: Hong
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabo
authors.forename: Lukas K
authors.initials: LK
authors.lastname: Tamm
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D001665:Binding Sites; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006860:Hydrogen Bonding; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D009997:Osmotic Pressure; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D000596:Amino Acids; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; D012492:Salts; C078167:OMPA outer membrane proteins