Identification, structure and mode of action of a new regulator of the Helicobacter pylori HP0525 ATPase.
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.
Hare
Stephen
S
School of Crystallography, Birkbeck College, London, UK.
Fischer
Wolfgang
W
Williams
Robert
R
Terradot
Laurent
L
Bayliss
Richard
R
Haas
Rainer
R
Waksman
Gabriel
G
D000244:Adenosine Diphosphate / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000201:enzymology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases