2CAD: Nikr From Helicobacter Pylori In Closed Trans-Conformation And Nickel Bound To 2f, 2x And 2i Sites

The survival of Helicobacter pylori in the human stomach critically relies on the availability and use of nickel, an absolute cofactor of the important virulence determinant urease. Nickel-responsive gene regulation is mediated by HpNikR, a protein belonging to the ribbon-helix-helix family of transcriptional regulators. Unlike its homologues, HpNikR acts as both a repressor and an activator within an acid adaptation cascade. We report the crystal structure of the full-length HpNikR in a nickel-free conformation and two nickel-bound structures obtained in different conditions: Ni1-HpNikR and Ni2-HpNikR. Apo-HpNikR shows the same global fold as its bacterial homologues although with an unusual closed trans-conformation and asymmetrical quaternary arrangement. The structure of Ni1-HpNikR in the presence of nickel has two different sides, one showing nickel binding similar to that of known NikRs and the other reflecting an intermediate state. The structure of Ni2-HpNikR obtained using a shorter exposure to nickel provides another snapshot of the nickel incorporation. Altogether, the three structures have allowed us to determine the route for nickel within HpNikR and reveal the cooperativity between the tetramerization domain and the DNA-binding domain. Experiments using point mutations of HpnikR residues involved in nickel internalisation confirm that these residues are critical for HpNikR functions in vivo.
PDB ID: 2CADDownload
MMDB ID: 86928
PDB Deposition Date: 2005/12/20
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 2CAD: tetrameric; determined by author and by software (PQS)
Molecular Components in 2CAD
Label Count Molecule
Proteins (4 molecules)
Putative Nickel-responsive Regulator(Gene symbol: HP1338)
Molecule annotation
Chemicals (22 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB