Back to Search
Start Over
Structure and function of theLeptospira interrogansperoxide stress regulator (PerR), an atypical PerR devoid of a structural metal-binding site
- Source :
- Journal of Biological Chemistry 2 (293), 497-509. (2018), Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2018, 293 (2), pp.497-509. ⟨10.1074/jbc.M117.804443⟩, Journal of Biological Chemistry, 2018, 293 (2), pp.497-509. ⟨10.1074/jbc.M117.804443⟩
- Publication Year :
- 2018
-
Abstract
- International audience; Peroxide sensing is essential for bacterial survival during aerobic metabolism and host infection. Peroxide stress regulators (PerRs) are homodimeric transcriptional repressors with each monomer typically containing both structural and regulatory metal-binding sites. PerR binding to gene promoters is controlled by the presence of iron in the regulatory site, and iron-catalyzed oxidation of PerR by H2O2 leads to the dissociation of PerR from DNA. In addition to a regulatory metal, most PerRs require a structural metal for proper dimeric assembly. We present here a structural and functional characterization of the PerR from the pathogenic spirochete Leptospira interrogans, a rare example of PerR lacking a structural metal-binding site. In vivo studies showed that the leptospiral PerR belongs to the peroxide stimulon in pathogenic species and is involved in controlling resistance to peroxide. Moreover, a perR mutant had decreased fitness in other host-related stress conditions, including at 37 °C or in the presence of superoxide anion. In vitro, leptospiral PerR could bind to the perR promoter region in a metal-dependent manner. The crystal structure of the leptospiral PerR revealed an asymmetric homodimer, with one monomer displaying complete regulatory metal coordination in the characteristic caliper-like DNA-binding conformation and the second monomer exhibiting disrupted regulatory metal coordination in an open non-DNA-binding conformation. This structure showed that leptospiral PerR assembles into a dimer in which a metal-induced conformational switch can occur independently in the two monomers. Our study demonstrates that structural metal binding is not compulsory for PerR dimeric assembly and for regulating peroxide stress.
- Subjects :
- MESH: Signal Transduction
0301 basic medicine
MESH: Leptospira interrogans
[SDV]Life Sciences [q-bio]
Mutant
Regulatory site
Metal Binding Site
Cell Cycle Proteins
spirochaetes
Biochemistry
Peroxide
chemistry.chemical_compound
Metalloprotein
oxidative stress
structural biology
spirochetes
MESH: Bacterial Proteins
Leptospira
chemistry.chemical_classification
biology
Chemistry
régulation transcriptionnelle
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
transcription regulation
Leptospira interrogans
Protein Binding
Signal Transduction
Repressor
Mitosis
PerR
reactive oxygen species (ROS)
Microbiology
03 medical and health sciences
MESH: Cell Cycle Proteins
Bacterial Proteins
métalloprotéine
MESH: Protein Binding
microbiologie
Molecular Biology
Binding Sites
metalloprotein
stress oxydatif
Cell Biology
MESH: Mitosis
biology.organism_classification
030104 developmental biology
MESH: Binding Sites
Structural biology
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry 2 (293), 497-509. (2018), Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2018, 293 (2), pp.497-509. ⟨10.1074/jbc.M117.804443⟩, Journal of Biological Chemistry, 2018, 293 (2), pp.497-509. ⟨10.1074/jbc.M117.804443⟩
- Accession number :
- edsair.doi.dedup.....22a1791136e69ce8ef074b3acbc923a3