title: Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator.
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.
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Zengqin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Manfeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Ana Carolina Dantas
authors.initials: AC
authors.lastname: Machado
authors.affiliation: Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Tsu-Pei
authors.initials: TP
authors.lastname: Chiu
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Jiangge
authors.initials: J
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Apicultural Research, Key Laboratory of Pollinating Insect Biology, Chinese Academy of Agricultural Science, Beijing 100093, China.
authors.forename: XinMei
authors.initials: X
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Chen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics*; D002942:Circular Dichroism; D003460:Crystallization; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D042201:Magnetospirillum; D046529:Microscopy, Electron, Transmission; D009875:Operator Regions, Genetic; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013057:Spectrum Analysis
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron