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  • The EMBO Journal (2007) 26, 4926 - 4934
  • doi:10.1038/sj.emboj.7601904

Published online: 1 November 2007

Identification, structure and mode of action of a new regulator of the Helicobacter pylori HP0525 ATPase

Stephen Hare1,2,a, Wolfgang Fischer3, Robert Williams1,2, Laurent Terradot1,2,b, Richard Bayliss1,2,c, Rainer Haas3 and Gabriel Waksman1,2

  1. School of Crystallography, Birkbeck College, London, UK
  2. Institute of Structural Molecular Biology at UCL/Birkbeck, London, UK
  3. Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München, Germany

Correspondence to:

Gabriel Waksman, School of Crystallography, Birkbeck College, Institute of Structural Molecular Biology at UCL/Birkbeck, Malet Street, London WC1E 7HX, UK. Tel.: +44 0207 631 6803; Fax: +44 0207 631 6803; E-mails: E-mail: g.waksman@bbk.ac.uk or g.waksman@ucl.ac.uk

aPresent address: Department of Infectious Diseases, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK

bPresent address: ESRF, CIBB, Macromolecular Crystallography Group, 38043 Grenoble Cedex, France

cPresent address: Section of Structural Biology, Institute of Cancer Research, Chester Beatty Labs, 237 Fulham Road, London SW3 6JB, UK

Received 22 May 2007; Accepted 4 October 2007

Helicobacter pylori is one of the world's most successful human pathogens causing gastric ulcers and cancers. A key virulence factor of H. pylori is the Cag pathogenicity island, which encodes a type IV secretion system. HP0525 is an essential component of the Cag system and acts as an inner membrane associated ATPase. HP0525 forms double hexameric ring structures, with the C-terminal domains (CTDs) forming a closed ring and the N-terminal domains (NTDs) forming a dynamic, open ring. Here, the crystal structure of HP0525 in complex with a fragment of HP1451, a protein of previously unknown function, is reported. The HP1451 construct consists of two domains similar to nucleic acid-binding domains. Two HP1451 molecules bind to the HP0525 NTDs on opposite sides of the hexamer, locking it in the closed form and forming a partial lid over the HP0525 chamber. From the structure, it is suggested that HP1451 acts as an inhibitory factor of HP0525 to regulate Cag-mediated secretion, a suggestion confirmed by results of in vitro ATPase assay and in vivo pull-down experiments.

  • Keywords:

    • ATPase,
    • crystal structure,
    • Helicobacter pylori,
    • type IV secretion,
    • VirB11