Structural Basis of the Nickel Response in Helicobacter pylori: Crystal Structures of HpNikR in Apo and Nickel-bound States
| Autor: | Cyril Dian, Agnès Labigne, Kristine Schauer, Laurent Terradot, Ulrike Kapp, Sean McSweeney |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular inorganic chemicals Protein Conformation Stereochemistry Blotting Western chemistry.chemical_element Repressor Cooperativity Biology Crystallography X-Ray Cofactor Bacterial Proteins Nickel Structural Biology Transcription (biology) otorhinolaryngologic diseases Molecular Biology Regulation of gene expression Helicobacter pylori Activator (genetics) Point mutation Recombinant Proteins DNA-Binding Proteins Repressor Proteins chemistry Structural Homology Protein Mutagenesis Site-Directed biology.protein |
| Zdroj: | Journal of Molecular Biology. 361:715-730 |
| ISSN: | 0022-2836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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