1. Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism
- Author
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Horne, Christopher R., Venugopal, Hariprasad, Panjikar, Santosh, Henrickson, Amy, Brookes, Emre, North, Rachel A., Murphy, James M., Friemann, Rosmarie, Griffin, Michael D.W., Ramm, Georg, Demeler, Borries, and Dobson, Renwick C.J.
- Subjects
0303 health sciences ,030306 microbiology ,Effector ,Chemistry ,Allosteric regulation ,Cooperative binding ,DNA-binding domain ,medicine.disease_cause ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,Transcription (biology) ,medicine ,Escherichia coli ,Gene ,DNA ,030304 developmental biology - 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. TheEscherichia coliGntR-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. Truncation of an N-terminal extension abolishes cooperative binding. The effector,N-acetylneuraminate, binds NanR and attenuates DNA binding. Crystal structure data show thatN-acetylneuraminate binding to NanR causes a domain rearrangement that locks the protein in a conformation that prevents DNA binding. Single-particle cryo-electron microscopy structures of NanR bound to DNA reveal the DNA binding domain is reorganized to engage DNA, while the three dimers assemble in close proximity across the (GGTATA)3-repeat operator allowing protein-protein interactions to formviathe N-terminal extensions. Our data provides a molecular basis for the regulation of bacterial sialic acid metabolism.
- Published
- 2020