6NZU

Structure of the human frataxin-bound iron-sulfur cluster assembly complex

6NZU の概要

• エントリーDOI: 10.2210/pdb6nzu/pdb
• EMDBエントリー: 0560 0561
• 分子名称: Cysteine desulfurase, mitochondrial, LYR motif-containing protein 4, Acyl carrier protein, ... (8 entities in total)
• 機能のキーワード: human frataxin-bound iron-sulfur cluster assembly complex, transferase, oxidoreductase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 185437.54

構造登録者

Fox, N.G.,Yu, X.,Xidong, F.,Alain, M.,Joseph, N.,Claire, S.D.,Christine, B.,Han, S.,Yue, W.W. (登録日: 2019-02-14, 公開日: 2019-05-22, 最終更新日: 2025-04-02)

主引用文献

Fox, N.G.,Yu, X.,Feng, X.,Bailey, H.J.,Martelli, A.,Nabhan, J.F.,Strain-Damerell, C.,Bulawa, C.,Yue, W.W.,Han, S.
Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.
Nat Commun, 10:2210-2210, 2019

PubMed Abstract: The core machinery for de novo biosynthesis of iron-sulfur clusters (ISC), located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by frataxin (FXN), scaffold protein ISCU, accessory protein ISD11, and acyl-carrier protein ACP. Deficiency in FXN leads to the loss-of-function neurodegenerative disorder Friedreich's ataxia (FRDA). Here the 3.2 Å resolution cryo-electron microscopy structure of the FXN-bound active human complex, containing two copies of the NFS1-ISD11-ACP-ISCU-FXN hetero-pentamer, delineates the interactions of FXN with other component proteins of the complex. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN. Our structure reveals how FXN facilitates ISC production through stabilizing key loop conformations of NFS1 and ISCU at the protein-protein interfaces, and suggests how FRDA clinical mutations affect complex formation and FXN activation.

PubMed: 31101807
DOI: 10.1038/s41467-019-09989-y

実験手法

ELECTRON MICROSCOPY (3.2 Å)