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HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes
- Source :
- Molecular Microbiology, Molecular Microbiology, 2014, 94 (2), pp.340-352. ⟨10.1111/mmi.12763⟩, Molecular Microbiology, Wiley, 2014, 94 (2), pp.340-352. ⟨10.1111/mmi.12763⟩
- Publication Year :
- 2014
-
Abstract
- International audience; Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways , some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO-haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mecha-nistic model for its dual regulatory role.
- Subjects :
- DNA, Bacterial
Models, Molecular
MESH: Operon
Protein Conformation
Heme
Crystallography, X-Ray
MESH: Leptospira
Regulon
MESH: Protein Conformation
MESH: Promoter Regions, Genetic
Operon
[CHIM.CRIS]Chemical Sciences/Cristallography
MESH: Protein Binding
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Promoter Regions, Genetic
Leptospira
MESH: Gene Expression Regulation, Bacterial
Binding Sites
MESH: Transcription Factors
Gene Expression Regulation, Bacterial
MESH: Crystallography, X-Ray
MESH: DNA, Bacterial
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
MESH: Binding Sites
MESH: Metabolic Networks and Pathways
MESH: Heme
MESH: Regulon
MESH: Models, Molecular
Metabolic Networks and Pathways
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 13652958 and 0950382X
- Volume :
- 94
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecular microbiology
- Accession number :
- edsair.pmid.dedup....5e00d1712092e101e193cbd954b892ed