5WKP

Crystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15A

5WKP の概要

• エントリーDOI: 10.2210/pdb5wkp/pdb
• 関連するPDBエントリー: 5WLW
• 分子名称: Cysteine desulfurase, mitochondrial, LYR motif-containing protein 4, Acyl carrier protein, ... (6 entities in total)
• 機能のキーワード: human mitochondrial cysteine desulfurse lyr motif containing protein 4 iron-sulfur cluster scaffold protein iscu1 acyl carrier protein 1 (e.coli), transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic: Cytoplasm: Q9Y697; Mitochondrion: Q9HD34; Cytoplasm : B7MJ81; Isoform 1: Mitochondrion . Isoform 2: Cytoplasm: Q9H1K1
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 162969.87

構造登録者

Boniecki, M.T.,Cygler, M. (登録日: 2017-07-25, 公開日: 2017-11-15, 最終更新日: 2023-10-04)

主引用文献

Boniecki, M.T.,Freibert, S.A.,Muhlenhoff, U.,Lill, R.,Cygler, M.
Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.
Nat Commun, 8:1287-1287, 2017

PubMed Abstract: Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.

PubMed: 29097656
DOI: 10.1038/s41467-017-01497-1

実験手法

X-RAY DIFFRACTION (3.15 Å)