Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism

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dc.contributor.authorHorne, Christoper R.
dc.contributor.authorVenugopal, Hariprasad
dc.contributor.authorPanjikar, Santosh
dc.contributor.authorWood, David M.
dc.contributor.authorHenrickson, Amy
dc.contributor.authorBrookes, Emre
dc.contributor.authorNorth, Rachel A.
dc.contributor.authorMurphy, James M.
dc.contributor.authorFriemann, Rosmarie
dc.contributor.authorGriffin, Michael D. W.
dc.contributor.authorRamm, Georg
dc.contributor.authorDemeler, Borries
dc.contributor.authorDobson, Renwick C. J.
dc.date.accessioned2021-06-24T21:36:34Z
dc.date.available2021-06-24T21:36:34Z
dc.date.issued2021
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesen_US
dc.description.abstractBacteria 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-reviewYesen_US
dc.identifier.citationHorne, 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/s41467-021-22253-6en_US
dc.identifier.urihttps://hdl.handle.net/10133/5917
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Centerburyen_US
dc.publisher.institutionMonash Universityen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionUniversity of Montanaen_US
dc.publisher.institutionUniversity of Melbourneen_US
dc.publisher.institutionSahlgrenska University Hospitalen_US
dc.publisher.institutionUniversity of Gothenburgen_US
dc.publisher.urlhttps://doi.org/10.1038/s41467-021-22253-6en_US
dc.subjectBiophysical methodsen_US
dc.subjectCryoelectron microscopyen_US
dc.subjectTranscriptionen_US
dc.subjectNanR
dc.subjectSialic acids
dc.subjectDNA binding
dc.subject.lcshDNA
dc.subject.lcshX-ray crystallography
dc.titleMechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolismen_US
dc.typeArticleen_US
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