title: Crystal structure of the Klebsiella pneumoniae NFeoB/FeoC complex and roles of FeoC in regulation of Fe2+ transport by the bacterial Feo system.
abstract: Feo is a transport system commonly used by bacteria to acquire environmental Fe(2+). It consists of three proteins: FeoA, FeoB, and FeoC. FeoB is a large protein with a cytosolic N-terminal domain (NFeoB) that contains a regulatory G protein domain and a helical S domain. The C-terminal region of FeoB is a transmembrane domain that likely acts as the Fe(2+) permease. NFeoB has been shown to form a trimer pore that may function as an Fe(2+) gate. FeoC is a small winged-helix protein that possesses four conserved cysteine residues with a consensus sequence that likely provides binding sites for the [Fe-S] cluster. Therefore, FeoC is presumed to be an [Fe-S] cluster-dependent regulator that directly controls transcription of the feo operon. Despite the apparent significance of the Feo system, however, the function of FeoC has not been experimentally demonstrated. Here, we show that Klebsiella pneumoniae FeoC (KpFeoC) forms a tight complex with the intracellular N-terminal domain of FeoB (KpNFeoB). The crystal structure of the complex reveals that KpFeoC binds to KpNFeoB between the switch II region of the G protein domain and the effector S domain and that the long KpFeoC W1 loop lies above the KpNFeoB nucleotide-binding site. These interactions suggest that KpFeoC modulates the guanine nucleotide-mediated signal transduction process. Moreover, we showed that binding of KpFeoC disrupts pore formation by interfering with KpNFeoB trimerization. These results provide strong evidence suggesting that KpFeoC plays a crucial role in regulating Fe(2+) transport in Klebsiella pneumonia in addition to the presumed gene regulator role.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Hung
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Tsai
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Juan
authors.forename: Yen-Lan
authors.initials: YL
authors.lastname: Hsu
authors.forename: Chwan-Deng
authors.initials: CD
authors.lastname: Hsiao
authors.forename: Tai-Huang
authors.initials: TH
authors.lastname: Huang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D007501:Iron / Q000378:metabolism*; D007711:Klebsiella pneumoniae / Q000737:chemistry* / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D007501:Iron