title: Revisiting the interaction between the chaperone Skp and lipopolysaccharide.
abstract: The bacterial outer membrane comprises two main classes of components, lipids and membrane proteins. These nonsoluble compounds are conveyed across the aqueous periplasm along specific molecular transport routes: the lipid lipopolysaccharide (LPS) is shuttled by the Lpt system, whereas outer membrane proteins (Omps) are transported by chaperones, including the periplasmic Skp. In this study, we revisit the specificity of the chaperone-lipid interaction of Skp and LPS. High-resolution NMR spectroscopy measurements indicate that LPS interacts with Skp nonspecifically, accompanied by destabilization of the Skp trimer and similar to denaturation by the nonnatural detergent lauryldimethylamine-N-oxide (LDAO). Bioinformatic analysis of amino acid conservation, structural analysis of LPS-binding proteins, and MD simulations further confirm the absence of a specific LPS binding site on Skp, making a biological relevance of the interaction unlikely. Instead, our analysis reveals a highly conserved salt-bridge network, which likely has a role for Skp function.
authors: Biozentrum, University of Basel, Basel, Switzerland. Electronic address: bjoern.burmann@unibas.ch.
authors: Björn M
authors: BM
authors: Burmann
authors: Bioinformatics Institute (A(∗)STAR), Singapore.
authors: Daniel A
authors: DA
authors: Holdbrook
authors: Biozentrum, University of Basel, Basel, Switzerland.
authors: Morgane
authors: M
authors: Callon
authors: Bioinformatics Institute (A(∗)STAR), Singapore; Department of Biological Sciences, National University of Singapore, Singapore.
authors: Peter J
authors: PJ
authors: Bond
authors: Biozentrum, University of Basel, Basel, Switzerland. Electronic address: sebastian.hiller@unibas.ch.
authors: Sebastian
authors: S
authors: Hiller
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D003902:Detergents / Q000737:chemistry; D004123:Dimethylamines / Q000737:chemistry; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D008070:Lipopolysaccharides / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011489:Protein Denaturation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D003902:Detergents; D004123:Dimethylamines; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; C072721:Skp protein, E coli; C014518:dodecyldimethylamine oxide