title: Structural analysis of the DNA-binding domain of the Helicobacter pylori response regulator ArsR.
abstract: The Helicobacter pylori ArsS-ArsR two-component signal transduction system, comprised of a sensor histidine kinase (ArsS) and a response regulator (ArsR), allows the bacteria to regulate gene expression in response to acidic pH. We expressed and purified the full-length ArsR protein and the DNA-binding domain of ArsR (ArsR-DBD), and we analyzed the tertiary structure of the ArsR-DBD using solution nuclear magnetic resonance (NMR) methods. Both the full-length ArsR and the ArsR-DBD behaved as monomers in size exclusion chromatography experiments. The structure of ArsR-DBD consists of an N-terminal four-stranded beta-sheet, a helical core, and a C-terminal beta-hairpin. The overall tertiary fold of the ArsR-DBD is most closely related to DBD structures of the OmpR/PhoB subfamily of bacterial response regulators. However, the orientation of the N-terminal beta-sheet with respect to the rest of the DNA-binding domain is substantially different in ArsR compared with the orientation in related response regulators. Molecular modeling of an ArsR-DBD-DNA complex permits identification of protein elements that are predicted to bind target DNA sequences and thereby regulate gene transcription in H. pylori.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37232, USA.
authors.forename: Shobhana S
authors.initials: SS
authors.lastname: Gupta
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Borin
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
authors.forename: Andrzej M
authors.initials: AM
authors.lastname: Krezel
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015534:Trans-Activators; D011494:Protein Kinases; D000071677:Histidine Kinase