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Structure paper

タイトル	Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.
ジャーナル・号・ページ	Nat Commun, Vol. 10, Issue 1, Page 2210, Year 2019
掲載日	2019年5月17日
著者	Nicholas G Fox / Xiaodi Yu / Xidong Feng / Henry J Bailey / Alain Martelli / Joseph F Nabhan / Claire Strain-Damerell / Christine Bulawa / Wyatt W Yue / Seungil Han /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:31101807 / PubMed Central
手法	EM (単粒子)
解像度	3.2 - 3.4 Å
構造データ	0560 6nzu EMDB-0560, PDB-6nzu: Structure of the human frataxin-bound iron-sulfur cluster assembly complex 手法: EM (単粒子) / 解像度: 3.2 Å EMDB-0561: Structure of the human frataxin-bound iron-sulfur cluster assembly complex 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-PLP: PYRIDOXAL-5'-PHOSPHATE / ピリドキサ-ル5′-りん酸 / ピリドキサールリン酸 ChemComp-8Q1: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate ChemComp-ZN: Unknown entry
由来	homo sapiens (ヒト) escherichia coli (大腸菌)
キーワード	TRANSFERASE (転移酵素) / OXIDOREDUCTASE (酸化還元酵素) / human frataxin-bound iron-sulfur cluster assembly complex