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

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-...

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Autores principales: Deng, Zengqin, Wang, Qing, Liu, Zhao, Zhang, Manfeng, Machado, Ana Carolina Dantas, Chiu, Tsu-Pei, Feng, Chong, Zhang, Qi, Yu, Lin, Qi, Lei, Zheng, Jiangge, Wang, Xu, Huo, XinMei, Qi, Xiaoxuan, Li, Xiaorong, Wu, Wei, Rohs, Remo, Li, Ying, Chen, Zhongzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506495/
https://www.ncbi.nlm.nih.gov/pubmed/26134419
http://dx.doi.org/10.1038/ncomms8642
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author Deng, Zengqin
Wang, Qing
Liu, Zhao
Zhang, Manfeng
Machado, Ana Carolina Dantas
Chiu, Tsu-Pei
Feng, Chong
Zhang, Qi
Yu, Lin
Qi, Lei
Zheng, Jiangge
Wang, Xu
Huo, XinMei
Qi, Xiaoxuan
Li, Xiaorong
Wu, Wei
Rohs, Remo
Li, Ying
Chen, Zhongzhou
author_facet Deng, Zengqin
Wang, Qing
Liu, Zhao
Zhang, Manfeng
Machado, Ana Carolina Dantas
Chiu, Tsu-Pei
Feng, Chong
Zhang, Qi
Yu, Lin
Qi, Lei
Zheng, Jiangge
Wang, Xu
Huo, XinMei
Qi, Xiaoxuan
Li, Xiaorong
Wu, Wei
Rohs, Remo
Li, Ying
Chen, Zhongzhou
author_sort Deng, Zengqin
collection PubMed
description 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.
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spelling pubmed-45064952015-07-21 Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator Deng, Zengqin Wang, Qing Liu, Zhao Zhang, Manfeng Machado, Ana Carolina Dantas Chiu, Tsu-Pei Feng, Chong Zhang, Qi Yu, Lin Qi, Lei Zheng, Jiangge Wang, Xu Huo, XinMei Qi, Xiaoxuan Li, Xiaorong Wu, Wei Rohs, Remo Li, Ying Chen, Zhongzhou Nat Commun Article 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. Nature Pub. Group 2015-07-02 /pmc/articles/PMC4506495/ /pubmed/26134419 http://dx.doi.org/10.1038/ncomms8642 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Deng, Zengqin
Wang, Qing
Liu, Zhao
Zhang, Manfeng
Machado, Ana Carolina Dantas
Chiu, Tsu-Pei
Feng, Chong
Zhang, Qi
Yu, Lin
Qi, Lei
Zheng, Jiangge
Wang, Xu
Huo, XinMei
Qi, Xiaoxuan
Li, Xiaorong
Wu, Wei
Rohs, Remo
Li, Ying
Chen, Zhongzhou
Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title_full Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title_fullStr Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title_full_unstemmed Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title_short Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
title_sort mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506495/
https://www.ncbi.nlm.nih.gov/pubmed/26134419
http://dx.doi.org/10.1038/ncomms8642
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