title: Structural insights into cardiolipin transfer from the Inner membrane to the outer membrane by PbgA in Gram-negative bacteria.
abstract: The outer membrane (OM) of Gram-negative bacteria is a unique asymmetric lipid bilayer in which the outer leaflet is composed of lipopolysaccharide (LPS) and the inner leaflet is formed by glycerophospholipid (GPL). The OM plays a fundamental role in protecting Gram-negative bacteria from harsh environments and toxic compounds. The transport and assembly pathways for phospholipids of bacterial OM are unknown. Cardiolipin (CL) plays an important role in OM biogenesis and pathogenesis, and the inner membrane (IM) protein PbgA, containing five transmembrane domains and a globular domain in periplasm has been recently identified as a CL transporter from the IM to the OM with an unknown mechanism. Here we present the first two crystal structures of soluble periplasmic globular domain of PbgA from S. typhimurium and E. coli, which revealed that the globular domains of PbgA resemble the structures of the arylsulfatase protein family and contains a novel core hydrophobic pocket that may be responsible for binding and transporting CLs. Our structural and functional studies shed an important light on the mechanism of CL transport in Gram-negative bacteria from the IM to the OM, which offers great potential for the development of novel antibiotics against multi-drug resistant bacterial infections.
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Haohao
authors.initials: H
authors.lastname: Dong
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Tang
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.|State Key Laboratory of Subtropical Bioresource Conservation and Utilization, Guangxi University, Nanning, Guangxi, 530004, China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Dong
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002308:Cardiolipins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008961:Models, Structural; D000072417:Protein Domains; D012486:Salmonella typhimurium / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002308:Cardiolipins; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins