title: An unusual crystal structure of ferric-enterobactin bound FepB suggests novel functions of FepB in microbial iron uptake.
abstract: Iron acquisition by siderophores is critical for the survival of most bacteria. Enterobactin is a kind of catechol siderophore that exhibits the highest affinity to iron atoms secreted by E. coli and several other species of Enterobacteriaceae. The periplasmic binding protein (PBP) FepB can transport ferric-enterobactin (Fe-Ent) from the outer membrane to the membrane-associated ATP-binding cassette transport system in E. coli. To elucidate this process, we solved the crystal structure of FepB in complex with Fe-Ent at a resolution of 1.8 Å. Consistent with previously reported NMR results, our crystal structure shows that, similar to the other type III PBPs, the FepB structure was folded with separated globular N- and C-termini linked by a long α-helix. Additionally, the structure showed that the Fe-Ent bound to the cleft between the N- and C-terminal domains. Exceptionally, FepB differs from the other known siderophore binding PBPs in that it forms a trimer by capturing four Fe-Ents that can each contribute to FepB trimerization. Dynamic light-scattering experiments are consistent with the structural observations and indicate that FepB forms a trimer in a Fe-Ent-dependent manner.
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China; State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China. Electronic address: bingqingsdu@163.com.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Yue
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Lichuan
authors.initials: L
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China. Electronic address: xu_sujuan@sdu.edu.cn.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Xu
mesh_terms: D001692:Biological Transport; D018360:Crystallography, X-Ray; D004758:Enterobactin / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D033903:Periplasmic Proteins / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D033903:Periplasmic Proteins; D011108:Polymers; C061266:fepB protein, E coli; D004758:Enterobactin; D007501:Iron
keywords: Crystal structure; Enterobactin uptake; FepB; Periplasmic binding protein