Structural highlights
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||
This page was last modified 06:46, 5 June 2014.