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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Circular oligomeric particles formed by Ros/MucR family members mediate DNA organization in α-proteobacteria
Antonio Chaves-Sanjuan1,2, Gianluca D'Abrosca3, Veronica Russo4
1Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy.
Abstract:
The transcriptional regulator MucR from Brucella species controls the expression of many genes, including those involved in virulence, by binding AT-rich DNA regions. MucR and its homologs belong to the Ros/MucR family, whose members occur in α-proteobacteria. MucR is a recent addition to the family of histone-like nucleoid structuring (H-NS) proteins. Indeed, despite the lack of sequence homology, MucR bears many functional similarities with H-NS and H-NS-like proteins, structuring the bacterial genome and acting as global regulators of transcription. Here we present an integrated cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance, modeling and biochemical study shedding light on the functional architecture of MucR from Brucella abortus and its homolog Ml5 from Mesorhizobium loti. We show that MucR and Ml5 fold in a circular quaternary assembly, which allows it to bridge and condense DNA by binding AT-rich sequences. Our results show that Ros/MucR family members are a novel type of H-NS-like proteins and, based on previous studies, provide a model connecting nucleoid structure and transcription regulation in α-proteobacteria.
Insights
The Ros/MucR protein family, including Brucella
Area of Science:
- Microbiology
- Molecular Biology
- Structural Biology
Background:
- The transcriptional regulator MucR controls virulence gene expression in Brucella by binding AT-rich DNA.
- MucR and homologs form the Ros/MucR family in α-proteobacteria, functionally resembling histone-like nucleoid structuring (H-NS) proteins.
- H-NS proteins globally regulate transcription by structuring the bacterial genome.
Purpose of the Study:
- To elucidate the functional architecture of MucR from Brucella abortus and its homolog Ml5 from Mesorhizobium loti.
- To understand how Ros/MucR family members function as novel H-NS-like proteins.
- To establish a model linking nucleoid structure and transcription regulation in α-proteobacteria.
Main Methods:
- Integrated cryogenic electron microscopy (cryo-EM).
- Nuclear magnetic resonance (NMR) spectroscopy.
- Molecular modeling.
- Biochemical assays.
Main Results:
- MucR and Ml5 form circular quaternary assemblies.
- These assemblies bridge and condense DNA by binding AT-rich sequences.
- Ros/MucR proteins represent a novel class of H-NS-like proteins.
Conclusions:
- MucR and Ml5 possess a unique circular quaternary structure enabling DNA binding and condensation.
- The Ros/MucR family are a novel type of H-NS-like proteins.
- This study provides a model for nucleoid structure and transcription regulation in α-proteobacteria.
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