4EC2

Crystal structure of trimeric frataxin from the yeast Saccharomyces cerevisiae, complexed with ferrous

4EC2 の概要

• エントリーDOI: 10.2210/pdb4ec2/pdb
• 関連するPDBエントリー: 2FQL 3OEQ 3OER
• 分子名称: Frataxin homolog, mitochondrial, FE (II) ION (2 entities in total)
• 機能のキーワード: alpha/beta sandwich, metallochaperone, iron-storage, transport protein
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• 細胞内の位置: Mitochondrion matrix : Q07540
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13727.03

構造登録者

Soderberg, C.A.G.,Rajan, S.,Gakh, O.,Isaya, G.,Al-Karadaghi, S. (登録日: 2012-03-26, 公開日: 2013-01-30, 最終更新日: 2023-09-13)

主引用文献

Soderberg, C.A.,Rajan, S.,Shkumatov, A.V.,Gakh, O.,Schaefer, S.,Ahlgren, E.C.,Svergun, D.I.,Isaya, G.,Al-Karadaghi, S.
The molecular basis of iron-induced oligomerization of frataxin and the role of the ferroxidation reaction in oligomerization.
J.Biol.Chem., 288:8156-8167, 2013

PubMed Abstract: The 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.

PubMed: 23344952
DOI: 10.1074/jbc.M112.442285

実験手法

X-RAY DIFFRACTION (3.002 Å)