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

Zengqin Deng, Qing Wang, Zhao Liu, Manfeng Zhang, Ana Carolina Dantas Machado, Tsu-Pei Chiu, Chong Feng, Qi Zhang, Lin Yu, Lei Qi, Jiangge Zheng, Xu Wang, XinMei Huo, Xiaoxuan Qi, Xiaorong Li, Wei Wu, Remo Rohs (), Ying Li () and Zhongzhou Chen ()
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Zengqin Deng: State Key Laboratory of Agrobiotechnology, China Agricultural University
Qing Wang: State Key Laboratory of Agrobiotechnology, China Agricultural University
Zhao Liu: Experimental Research Center, China Academy of Chinese Medical Sciences
Manfeng Zhang: State Key Laboratory of Agrobiotechnology, China Agricultural University
Ana Carolina Dantas Machado: Molecular and Computational Biology Program, Chemistry, Physics, and Computer Science, University of Southern California
Tsu-Pei Chiu: Molecular and Computational Biology Program, Chemistry, Physics, and Computer Science, University of Southern California
Chong Feng: State Key Laboratory of Agrobiotechnology, China Agricultural University
Qi Zhang: State Key Laboratory of Agrobiotechnology, China Agricultural University
Lin Yu: State Key Laboratory of Agrobiotechnology, China Agricultural University
Lei Qi: State Key Laboratory of Agrobiotechnology, China Agricultural University
Jiangge Zheng: State Key Laboratory of Agrobiotechnology, China Agricultural University
Xu Wang: State Key Laboratory of Agrobiotechnology, China Agricultural University
XinMei Huo: Institute of Apicultural Research, Key Laboratory of Pollinating Insect Biology, Chinese Academy of Agricultural Science
Xiaoxuan Qi: State Key Laboratory of Agrobiotechnology, China Agricultural University
Xiaorong Li: State Key Laboratory of Agrobiotechnology, China Agricultural University
Wei Wu: State Key Laboratory of Agrobiotechnology, China Agricultural University
Remo Rohs: Molecular and Computational Biology Program, Chemistry, Physics, and Computer Science, University of Southern California
Ying Li: State Key Laboratory of Agrobiotechnology, China Agricultural University
Zhongzhou Chen: State Key Laboratory of Agrobiotechnology, China Agricultural University

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8642

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