Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex

被引:144
作者
Boniecki, Michal T. [1 ]
Freibert, Sven A. [2 ]
Muehlenhoff, Ulrich [2 ]
Lill, Roland [2 ,3 ]
Cygler, Miroslaw [1 ,4 ]
机构
[1] Univ Saskatchewan, Dept Biochem, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada
[2] Philipps Univ, Inst Zytobiol & Zytopathol, Robert Koch Str 6, D-35032 Marburg, Germany
[3] LOEWE Zentrum Synthet Mikrobiol SynMikro, Hans Meerwein Str, D-35043 Marburg, Germany
[4] McGill Univ, Dept Biochem, 3649 Promenade Sir William Osler, Montreal, PQ H3G 0B1, Canada
来源
NATURE COMMUNICATIONS | 2017年 / 8卷
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
IRON-SULFUR CLUSTER; ACYL CARRIER PROTEIN; CYSTEINE DESULFURASE; ESCHERICHIA-COLI; X-RAY; ARABIDOPSIS-THALIANA; CRYSTAL-STRUCTURE; SCAFFOLD PROTEIN; BIOGENESIS; FRATAXIN;
D O I
10.1038/s41467-017-01497-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:15
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