title: Solution Structure and Dynamics of LptE from Pseudomonas aeruginosa.
abstract: LptE is an outer membrane (OM) lipoprotein found in Gram-negative bacteria, where it forms a complex with the β-barrel lipopolysaccharide (LPS) transporter LptD. The LptD/E complex plays a key role in OM biogenesis, by translocating newly synthesized LPS molecules from the periplasm into the external leaflet of the asymmetric OM during cell growth. The LptD/E complex in Pseudomonas aeruginosa (Pa) is a target for macrocyclic β-hairpin-shaped peptidomimetic antibiotics, which inhibit the transport of LPS to the cell surface. So far, the three-dimensional structure of the Pa LptD/E complex and the mode of interaction with these antibiotics are unknown. Here, we report the solution structure of a Pa LptE derivative lacking the N-terminal lipid membrane anchor, determined by multidimensional solution nuclear magnetic resonance (NMR) spectroscopy. The structure reveals a central five-stranded β-sheet against which pack a long C-terminal and a short N-terminal α-helix, as found in homologues of LptE from other Gram-negative bacteria. One unique feature is an extended C-terminal helix in Pa LptE, which in a model of the Pa LptD/E complex appears to be long enough to contact the periplasmic domain of LptD. Chemical shift mapping experiments suggest only weak interactions occur between LptE and the oligosaccharide chains of LPS. The NMR structure of Pa LptE will be valuable for more detailed structural studies of the LptD/E complex from P. aeruginosa.
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Moehle
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Harsha
authors.initials: H
authors.lastname: Kocherla
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Bacsa
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Jurt
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Zerbe
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: John A
authors.initials: JA
authors.lastname: Robinson
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zerbe
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019897:Periplasm / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D012996:Solutions
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D012996:Solutions