title: Structure of the cholera toxin secretion channel in its closed state.
abstract: The type II secretion system (T2SS) is a macromolecular complex spanning the inner and outer membranes of Gram-negative bacteria. Remarkably, the T2SS secretes folded proteins, including multimeric assemblies such as cholera toxin and heat-labile enterotoxin from Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. The major outer membrane T2SS protein is the 'secretin' GspD. Cryo-EM reconstruction of the V. cholerae secretin at 19-Å resolution reveals a dodecameric structure reminiscent of a barrel, with a large channel at its center that contains a closed periplasmic gate. The GspD periplasmic domain forms a vestibule with a conserved constriction, and it binds to a pentameric exoprotein and to the trimeric tip of the T2SS pseudopilus. By combining our results with structures of the cholera toxin and T2SS pseudopilus tip, we provide a structural basis for a possible secretion mechanism of the T2SS.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Steve L
authors.initials: SL
authors.lastname: Reichow
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Korotkov
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Hol
authors.forename: Tamir
authors.initials: T
authors.lastname: Gonen
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002772:Cholera Toxin / Q000378:metabolism; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D010861:Fimbriae, Bacterial / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019897:Periplasm / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014734:Vibrio cholerae / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D001425:Bacterial Outer Membrane Proteins; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin