Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism
- Author(s)
- Horne, CR; Venugopal, H; Panjikar, S; Wood, DM; Henrickson, A; Brookes, E; North, RA; Murphy, JM; Friemann, R; Griffin, MDW; Ramm, G; Demeler, B; Dobson, RCJ;
- Details
- Publication Year 2021-03-31,Volume 12,Issue #1,Page 1988
- Journal Title
- Nature Communications
- 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.
- Publisher
- NPG
- Research Division(s)
- Inflammation
- PubMed ID
- 33790291
- Publisher's Version
- https://doi.org/10.1038/s41467-021-22253-6
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-021-22253-6. - Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-04-28 08:15:50
Last Modified: 2021-05-06 08:56:31