Premium
Identification, structure and mode of action of a new regulator of the Helicobacter pylori HP0525 ATPase
Author(s) -
Hare Stephen,
Fischer Wolfgang,
Williams Robert,
Terradot Laurent,
Bayliss Richard,
Haas Rainer,
Waksman Gabriel
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601904
Subject(s) - biology , regulator , helicobacter pylori , identification (biology) , atpase , mode of action , computational biology , genetics , microbiology and biotechnology , biochemistry , enzyme , gene , ecology
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.