Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22253-6
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Funding
- Biomolecular Interaction Centre (University of Canterbury)
- Canterbury Medical Research Foundation
- Maurice Wilkins Centre
- New Zealand Royal Society Marsden Fund [UOC1506]
- Ministry of Business, Innovation and Employment Smart Ideas grant [UOCX1706]
- ARC LIEF grants [LE120100090, LE200100045]
- Swedish Governmental Agency for Innovation Systems [2017-00180]
- Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg
- NHMRC [1172929, 9000653]
- Victorian Government Operational Infrastructure Support Scheme
- NIH [GM120600, NSF-ACI-1339649]
- NSF/XSEDE [TG-MCB070039N]
- University of Texas [TG457201]
- Canada Foundation for Innovation [CFI-37589]
- Australian Research Council [LE200100045, LE120100090] Funding Source: Australian Research Council
- National Health and Medical Research Council of Australia [9000653, 1172929] Funding Source: NHMRC
- Swedish Research Council [2017-00180] Funding Source: Swedish Research Council
- Vinnova [2017-00180] Funding Source: Vinnova
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This study provides a detailed molecular basis for the regulation of bacterial sialic acid metabolism by the GntR-type transcriptional repressor NanR. The authors used biophysical analysis and structural biology to reveal how NanR binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.
Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA)(3)-repeat operator cooperatively and with high affinity. Single-particle cryo-electron microscopy structures reveal the DNA-binding domain is reorganized to engage DNA, while three dimers assemble in close proximity across the (GGTATA)(3)-repeat operator. Such an interaction allows cooperative protein-protein interactions between NanR dimers via their N-terminal extensions. The effector, N-acetylneuraminate, binds NanR and attenuates the NanR-DNA interaction. The crystal structure of NanR in complex with N-acetylneuraminate reveals a domain rearrangement upon N-acetylneuraminate binding to lock NanR in a conformation that weakens DNA binding. Our data provide a molecular basis for the regulation of bacterial sialic acid metabolism. The GntR superfamily is one of the largest families of transcription factors in prokaryotes. Here the authors combine biophysical analysis and structural biology to dissect the mechanism by which NanR - a GntR-family regulator - binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.
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