Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism.
Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism.
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NanR基因抑制和变构诱导细菌唾液酸代谢的机制。
DOI：
10.1038/s41467-021-22253-6
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发表时间：
2021-03-31
影响因子：
16.6
通讯作者：
Dobson RCJ
中科院分区：
文献类型：
--
作者：
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
细菌对环境变化的反应是诱导某些基因的转录并抑制其他基因。唾液酸覆盖在人体细胞表面，是致病菌和寄生菌的营养来源。大肠杆菌GntR型转录抑制因子NanR调节唾液酸代谢，但其机制尚不清楚。在这里，我们证明了三个NanR二聚体结合（GGTATA）3-重复操作合作，并具有高亲和力。单粒子冷冻电子显微镜结构显示DNA结合结构域被重组以接合DNA，而三个二聚体在（GGTATA）3-重复操作子附近组装。这种相互作用允许NanR二聚体之间通过其N-末端延伸的协同蛋白质-蛋白质相互作用。效应物N-乙酰神经氨酸结合NanR并减弱NanR-DNA相互作用。与N-乙酰神经氨酸复合的NanR的晶体结构揭示了N-乙酰神经氨酸结合后的结构域重排，以将NanR锁定在削弱DNA结合的构象中。我们的研究结果为唾液酸代谢的调控提供了分子基础。GntR超家族是原核生物中最大的转录因子家族之一。在这里，作者结合联合收割机生物物理分析和结构生物学来剖析NanR -GntR家族调节因子-结合其启动子以抑制唾液酸代谢所需基因转录的机制。
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. The GntR superfamily is one of the largest families of transcription factors in prokaryotes. Here the authors combine biophysical analysis and structural biology to dissect the mechanism by which NanR — a GntR-family regulator — binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Fillenberg, Simon B.;Grau, Florian C.;Muller, Yves A.
通讯作者：
Muller, Yves A.
影响因子：
2.4
作者：
Demeler, Borries;Brookes, Emre
通讯作者：
Brookes, Emre
影响因子：
3.4
作者：
Baos, S. C.;Phillips, D. B.;Berry, M.
通讯作者：
Berry, M.
影响因子：
14.9
作者：
Gao YG;Suzuki H;Itou H;Zhou Y;Tanaka Y;Wachi M;Watanabe N;Tanaka I;Yao M
通讯作者：
Yao M