title: Disulfide rearrangement triggered by translocon assembly controls lipopolysaccharide export.
abstract: The presence of lipopolysaccharide (LPS) on the cell surface of Gram-negative bacteria is critical for viability. A conserved β-barrel membrane protein LptD (lipopolysaccharide transport protein D) translocates LPS from the periplasm across the outer membrane (OM). In Escherichia coli, this protein contains two disulfide bonds and forms the OM LPS translocon with the lipoprotein LptE. Here, we identified seven in vivo states on the oxidative-folding pathway of LptD. Proper assembly involved a nonfunctional intermediate containing non-native disulfides. Intermediate formation required the oxidase DsbA, and subsequent maturation to the active form with native disulfides was triggered by LptE. Thus, disulfide bond-dependent protein folding of LptD requires the proper assembly of a two-protein complex to promote disulfide bond rearrangement.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Shu-Sin
authors.initials: SS
authors.lastname: Chng
authors.forename: Mingyu
authors.initials: M
authors.lastname: Xue
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Garner
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kadokura
authors.forename: Dana
authors.initials: D
authors.lastname: Boyd
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beckwith
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahne
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D003553:Cystine / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; C475958:LptD protein, E coli; C514179:LptE protein, E coli; D003553:Cystine; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli