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-Structure paper
タイトル | Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 1988, Year 2021 |
掲載日 | 2021年3月31日 |
著者 | Christopher R Horne / Hariprasad Venugopal / Santosh Panjikar / David M Wood / Amy Henrickson / Emre Brookes / Rachel A North / James M Murphy / Rosmarie Friemann / Michael D W Griffin / Georg Ramm / Borries Demeler / Renwick C J Dobson / |
PubMed 要旨 | 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 ...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)-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)-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. |
リンク | Nat Commun / PubMed:33790291 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.9 - 8.3 Å |
構造データ | EMDB-21652, PDB-6wfq: EMDB-21661: Hexameric NanR-DNA hetero-complex |
由来 |
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キーワード | GENE REGULATION / NanR dimer-DNA hetero-complex / transcriptional regulator / GntR superfamily / sialic acid / Neu5Ac / cooperativity. / cooperativity / Gene regulation. |