Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator

文献类型: 外文期刊

第一作者: Deng, Zengqin

作者: Deng, Zengqin;Wang, Qing;Zhang, Manfeng;Feng, Chong;Zhang, Qi;Yu, Lin;Qi, Lei;Zheng, Jiangge;Wang, Xu;Qi, Xiaoxuan;Li, Xiaorong;Wu, Wei;Li, Ying;Chen, Zhongzhou;Liu, Zhao;Machado, Ana Carolina Dantas;Chiu, Tsu-Pei;Rohs, Remo;Machado, Ana Carolina Dantas;Chiu, Tsu-Pei;Rohs, Remo;Machado, Ana Carolina Dantas;Chiu, Tsu-Pei;Rohs, Remo;Machado, Ana Carolina Dantas;Chiu, Tsu-Pei;Rohs, Remo;Huo, XinMei

作者机构:

关键词: PROTEIN-DNA RECOGNITION;IRON-BINDING SITE;MAGNETOSPIRILLUM-GRYPHISWALDENSE;ESCHERICHIA-COLI;X-RAY;PSEUDOMONAS-AERUGINOSA;MAGNETOSOME FORMATION;CRYSTAL-STRUCTURE;FUR PROTEIN;REPRESSOR

期刊名称:NATURE COMMUNICATIONS ( 影响因子:14.919; 五年影响因子:15.805 )

ISSN:

年卷期:

页码:

收录情况: SCI

摘要: Ferric uptake regulator (Fur) plays a key role in the iron homeostasis of prokaryotes, such as bacterial pathogens, but the molecular mechanisms and structural basis of Fur-DNA binding remain incompletely understood. Here, we report high-resolution structures of Magnetospirillum gryphiswaldense MSR-1 Fur in four different states: apo-Fur, holo-Fur, the Fur-feoAB1 operator complex and the Fur-Pseudomonas aeruginosa Fur box complex. Apo-Fur is a transition metal ion-independent dimer whose binding induces profound conformational changes and confers DNA-binding ability. Structural characterization, mutagenesis, biochemistry and in vivo data reveal that Fur recognizes DNA by using a combination of base readout through direct contacts in the major groove and shape readout through recognition of the minor-groove electrostatic potential by lysine. The resulting conformational plasticity enables Fur binding to diverse substrates. Our results provide insights into metal ion activation and substrate recognition by Fur that suggest pathways to engineer magnetotactic bacteria and antipathogenic drugs.

分类号: N

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