Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism
dc.contributor.author | Horne, Christoper R. | |
dc.contributor.author | Venugopal, Hariprasad | |
dc.contributor.author | Panjikar, Santosh | |
dc.contributor.author | Wood, David M. | |
dc.contributor.author | Henrickson, Amy | |
dc.contributor.author | Brookes, Emre | |
dc.contributor.author | North, Rachel A. | |
dc.contributor.author | Murphy, James M. | |
dc.contributor.author | Friemann, Rosmarie | |
dc.contributor.author | Griffin, Michael D. W. | |
dc.contributor.author | Ramm, Georg | |
dc.contributor.author | Demeler, Borries | |
dc.contributor.author | Dobson, Renwick C. J. | |
dc.date.accessioned | 2021-06-24T21:36:34Z | |
dc.date.available | 2021-06-24T21:36:34Z | |
dc.date.issued | 2021 | |
dc.description | Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) applies | en_US |
dc.description.abstract | 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. | en_US |
dc.description.peer-review | Yes | en_US |
dc.identifier.citation | Horne, C. R., Venogopal, H., Panjikar, S., Wood, D. M., Henrickson, A., Brookes, E., North, R. A., Murphy, J. M., Friemann, R., Griffin, M. D., Ramm, G., Demeler, B., & Dobson, R. C. J. (2021). Mechanism of NanR gene repression and allosteric inducation of bacterial sialic acid metabolism. Nature Communications, 12, Article1988 (2021). https://doi.org/10.1038/s41467-021-22253-6 | en_US |
dc.identifier.uri | https://hdl.handle.net/10133/5917 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.publisher.department | Department of Chemistry and Biochemistry | en_US |
dc.publisher.faculty | Arts and Science | en_US |
dc.publisher.institution | University of Centerbury | en_US |
dc.publisher.institution | Monash University | en_US |
dc.publisher.institution | University of Lethbridge | en_US |
dc.publisher.institution | University of Montana | en_US |
dc.publisher.institution | University of Melbourne | en_US |
dc.publisher.institution | Sahlgrenska University Hospital | en_US |
dc.publisher.institution | University of Gothenburg | en_US |
dc.publisher.url | https://doi.org/10.1038/s41467-021-22253-6 | en_US |
dc.subject | Biophysical methods | en_US |
dc.subject | Cryoelectron microscopy | en_US |
dc.subject | Transcription | en_US |
dc.subject | NanR | |
dc.subject | Sialic acids | |
dc.subject | DNA binding | |
dc.subject.lcsh | DNA | |
dc.subject.lcsh | X-ray crystallography | |
dc.title | Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism | en_US |
dc.type | Article | en_US |