4ec2 | pdb_00004ec2
Crystal structure of trimeric frataxin from the yeast Saccharomyces cerevisiae, complexed with ferrous
Structural highlights
Function[FRDA_YEAST] Promotes the biosynthesis of heme as well as the assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. Plays a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+). Can store large amounts of the metal in the form of a ferrihydrite mineral by oligomerization. May be involved in regulation of the mitochondrial electron transport chain.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe role of the mitochondrial protein frataxin in iron storage and detoxification, iron delivery to iron-sulfur cluster biosynthesis, heme biosynthesis, and aconitase repair has been extensively studied during the last decade. However, still no general consensus exists on the details of the mechanism of frataxin function and oligomerization. Here, using small-angle x-ray scattering and x-ray crystallography, we describe the solution structure of the oligomers formed during the iron-dependent assembly of yeast (Yfh1) and Escherichia coli (CyaY) frataxin. At an iron-to-protein ratio of 2, the initially monomeric Yfh1 is converted to a trimeric form in solution. The trimer in turn serves as the assembly unit for higher order oligomers induced at higher iron-to-protein ratios. The x-ray crystallographic structure obtained from iron-soaked crystals demonstrates that iron binds at the trimer-trimer interaction sites, presumably contributing to oligomer stabilization. For the ferroxidation-deficient D79A/D82A variant of Yfh1, iron-dependent oligomerization may still take place, although >50% of the protein is found in the monomeric state at the highest iron-to-protein ratio used. This demonstrates that the ferroxidation reaction controls frataxin assembly and presumably the iron chaperone function of frataxin and its interactions with target proteins. For E. coli CyaY, the assembly unit of higher order oligomers is a tetramer, which could be an effect of the much shorter N-terminal region of this protein. The results show that understanding of the mechanistic features of frataxin function requires detailed knowledge of the interplay between the ferroxidation reaction, iron-induced oligomerization, and the structure of oligomers formed during assembly. The molecular basis of iron-induced oligomerization of frataxin and the role of the ferroxidation reaction in oligomerization.,Soderberg CA, Rajan S, Shkumatov AV, Gakh O, Schaefer S, Ahlgren EC, Svergun DI, Isaya G, Al-Karadaghi S J Biol Chem. 2013 Mar 22;288(12):8156-67. doi: 10.1074/jbc.M112.442285. Epub 2013, Jan 23. PMID:23344952[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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