· S. Hare, W. Fisher, R. Williams, L.
Terradot, R. Bayliss, R. Haas, and G. Waksman.
Identification,
structure and mode of action of a new regulator of the Helicobacter pylori HP0525
ATPase
EMBO Journal. 26(23):4926-34 (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 (CTD) forming a closed ring and the N-terminal domains (NTD) 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.