title: Redox sensing molecular mechanism of an iron metabolism regulatory protein FBXL5.
abstract: FBXL5 is a subunit of the SCFFBXL5ubiquitin ligase complex that targets the proteasomal degradation of iron regulatory protein IRP2, which is an important regulator in iron metabolism. The degradation of FBXL5 itself is regulated in an iron- and oxygen-responsive manner through its diiron center containing Hr-like domain. Although the crystal structure of the Hr-like domain of FBXL5 and its degradation based on iron/oxygen sensing has been reported, the redox sensing molecular mechanism is still not clear. Herein the redox properties of FBXL5 were investigated via EPR, direct electrochemistry, SRCD, fluorescence emission spectroscopy, and redox kinetics. The results indicated that the conformation and function of FBXL5 are tuned by the redox states of the diiron center. The redox reactions of the diiron center are accompanied with conformational changes and iron release, which are associated with FBXL5 stability and degradation. These results provide insights into the redox sensing mechanism by which FBXL5 can serve as an iron metabolism regulator within mammalian cells.
authors.affiliation: Department of Chemistry & Shanghai Key Laboratory of Chemical Biology for Protein Research, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Yaozhu
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Chemistry & Shanghai Key Laboratory of Chemical Biology for Protein Research, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Chemistry & Shanghai Key Laboratory of Chemical Biology for Protein Research, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Pengbiao
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Chemistry & Shanghai Key Laboratory of Chemical Biology for Protein Research, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China. Electronic address: xstan@fudan.edu.cn.
authors.forename: Xiangshi
authors.initials: X
authors.lastname: Tan
mesh_terms: D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry; D035925:Iron-Regulatory Proteins / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D000072417:Protein Domains; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017356:Synchrotrons; D014364:Tryptophan / Q000737:chemistry; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry*
chemical_list: D044783:F-Box Proteins; C521741:FBXL5 protein, human; D035925:Iron-Regulatory Proteins; D014364:Tryptophan; D007501:Iron; D043743:Ubiquitin-Protein Ligase Complexes; D010100:Oxygen
keywords: FBXL5; Iron metabolism; Redox sensing