3v5z | pdb_00003v5z
Structure of FBXL5 hemerythrin domain, C2 cell, grown anaerobically
Structural highlights
FunctionFBXL5_HUMAN Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. Upon high iron and oxygen level, it specifically recognizes and binds IREB2/IRP2, promoting its ubiquitination and degradation by the proteasome. Promotes ubiquitination and subsequent degradation of DCTN1/p150-glued.[1] [2] [3] Publication Abstract from PubMedMammalian cells maintain iron homeostasis by sensing changes in bioavailable iron levels and promoting adaptive responses. FBXL5 is a subunit of an E3 ubiquitin ligase complex that mediates the stability of Iron Regulatory Protein 2, an important posttranscriptional regulator of several genes involved in iron metabolism. FBXL5's own stability is regulated in an iron- and oxygen-responsive manner, contingent upon the presence of its N-terminal domain. Here we present the atomic structure of FBXL5's N-terminus, a hemerythrin-like alpha-helical bundle fold not previously observed in mammalian proteins. The core of this domain employs an unusual assortment of amino acids necessary for the assembly and sensing properties of its diiron center. These regulatory features govern the accessibility of a mapped sequence required for proteasomal degradation of FBXL5. Detailed molecular and structural characterization of the ligand responsive hemerythrin domain provides insights into the mechanisms by which FBXL5 serves as a unique mammalian metabolic sensor. Structural and molecular characterization of the iron-sensing hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5).,Thompson JW, Salahudeen AA, Chollangi S, Ruiz JC, Brautigam CA, Makris TM, Lipscomb JD, Tomchick DR, Bruick RK J Biol Chem. 2012 Jan 17. PMID:22253436[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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