基于交联质谱和小角 X 射线散射的人线粒体半胱氨酸脱硫酶复合物的结构特征。
Architectural Features of Human Mitochondrial Cysteine Desulfurase Complexes from Crosslinking Mass Spectrometry and Small-Angle X-Ray Scattering.
机构信息
Biochemistry Department, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
Biochemistry Department, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
出版信息
Structure. 2018 Aug 7;26(8):1127-1136.e4. doi: 10.1016/j.str.2018.05.017. Epub 2018 Jul 5.
Abstract
Cysteine desulfurase plays a central role in mitochondrial iron-sulfur cluster biogenesis by generating sulfur through the conversion of L-cysteine to L-alanine and by serving as the platform for assembling other components of the biosynthetic machinery, including ISCU, frataxin, and ferredoxin. The human mitochondrial cysteine desulfurase complex consists of two copies each of NFS1, ISD11, and acyl carrier protein. We describe results from chemical crosslinking coupled with tandem mass spectrometry and small-angle X-ray scattering studies that are consistent with a closed NFS1 dimer rather than an open one for both the cysteine desulfurase-ISCU and cysteine desulfurase-ISCU-frataxin complexes. We present a structural model for the cysteine desulfurase-ISCU-frataxin complex derived from chemical crosslinking restraints in conjunction with the recent crystal structure of the cysteine desulfurase-ISCU-zinc complex and distance constraints from nuclear magnetic resonance.
摘要
半胱氨酸脱硫酶通过将 L-半胱氨酸转化为 L-丙氨酸来产生硫，并且作为组装生物合成机制其他组件（包括 ISCU、 frataxin 和铁氧还蛋白）的平台，在线粒体铁硫簇生物发生中发挥核心作用。人线粒体半胱氨酸脱硫酶复合物由两个 NFS1、ISD11 和酰基载体蛋白的拷贝组成。我们描述了化学交联与串联质谱和小角 X 射线散射研究相结合的结果，这些结果与胱氨酸脱硫酶-ISC 和胱氨酸脱硫酶-ISC-frataxin 复合物的封闭 NFS1 二聚体而不是开放二聚体一致。我们提出了一个基于胱氨酸脱硫酶-ISC-frataxin 复合物的结构模型，该模型源自化学交联约束，并结合了最近的胱氨酸脱硫酶-ISC-锌复合物的晶体结构和来自核磁共振的距离约束。
相似文献
1
Architectural Features of Human Mitochondrial Cysteine Desulfurase Complexes from Crosslinking Mass Spectrometry and Small-Angle X-Ray Scattering.基于交联质谱和小角 X 射线散射的人线粒体半胱氨酸脱硫酶复合物的结构特征。
Structure. 2018 Aug 7;26(8):1127-1136.e4. doi: 10.1016/j.str.2018.05.017. Epub 2018 Jul 5.
2
Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.线粒体 Fe/S 簇合成复合物的结构与功能动态
Nat Commun. 2017 Nov 3;8(1):1287. doi: 10.1038/s41467-017-01497-1.
3
Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis.人类线粒体铁氧化还原蛋白1（FDX1）和铁氧化还原蛋白2（FDX2）均与半胱氨酸脱硫酶结合，并为铁硫簇生物合成提供电子。
Biochemistry. 2017 Jan 24;56(3):487-499. doi: 10.1021/acs.biochem.6b00447. Epub 2017 Jan 11.
4
The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with l-Cysteine Desulfurase NFS1.铁硫簇组装因子ISD11的N端对于亚细胞定位及与L-半胱氨酸脱硫酶NFS1的相互作用至关重要。
Biochemistry. 2017 Mar 28;56(12):1797-1808. doi: 10.1021/acs.biochem.6b01239. Epub 2017 Mar 17.
5
Mitochondrial Cysteine Desulfurase and ISD11 Coexpressed in Escherichia coli Yield Complex Containing Acyl Carrier Protein.线粒体半胱氨酸脱硫酶与ISD11在大肠杆菌中共表达产生含酰基载体蛋白的复合物。
ACS Chem Biol. 2017 Apr 21;12(4):918-921. doi: 10.1021/acschembio.6b01005. Epub 2017 Mar 2.
6
Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery.人类线粒体铁硫簇组装机制的结构
J Biol Chem. 2016 Sep 30;291(40):21296-21321. doi: 10.1074/jbc.M116.738542. Epub 2016 Aug 12.
7
Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.人 Fe-S 组装亚基的结构揭示了出乎意料的半胱氨酸脱硫酶结构和酰基-ACP-ISD11 相互作用。
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5325-E5334. doi: 10.1073/pnas.1702849114. Epub 2017 Jun 20.
8
Structural and functional characterization of a frataxin from a thermophilic organism.热嗜菌鱼降钙素原的结构与功能特征分析。
FEBS J. 2019 Feb;286(3):495-506. doi: 10.1111/febs.14750. Epub 2019 Jan 30.
9
Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity.锌（II）与人源野生型 ISCU 和 Met140 变体结合可调节 NFS1 脱硫酶活性。
Biochimie. 2018 Sep;152:211-218. doi: 10.1016/j.biochi.2018.07.012. Epub 2018 Jul 20.
10
Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly.铁蛋白直接通过暴露底物结合位点来刺激线粒体半胱氨酸脱硫酶，并且具有铁蛋白规避能力的突变 Fe-S 簇支架蛋白以类似的方式起作用。
J Biol Chem. 2013 Dec 27;288(52):36773-86. doi: 10.1074/jbc.M113.525857. Epub 2013 Nov 11.
引用本文的文献
1
Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis.铁调素捕获低丰度四级结构以刺激人类铁硫簇生物合成。
Biochemistry. 2025 Feb 18;64(4):903-916. doi: 10.1021/acs.biochem.4c00733. Epub 2025 Feb 5.
2
Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2.在 ISCU2 上从头组装 [2Fe-2S] 簇过程中硫转移的机制和结构动力学。
Nat Commun. 2024 Apr 16;15(1):3269. doi: 10.1038/s41467-024-47310-8.
3
Mammalian mitochondrial iron-sulfur cluster biogenesis and transfer and related human diseases.哺乳动物线粒体铁硫簇的生物合成与转移及相关人类疾病
Biophys Rep. 2021 Apr 30;7(2):127-141. doi: 10.52601/bpr.2021.200038.
4
Mammalian iron sulfur cluster biogenesis: From assembly to delivery to recipient proteins with a focus on novel targets of the chaperone and co-chaperone proteins.哺乳动物铁硫簇生物合成：从组装到传递给受体蛋白，重点关注伴侣蛋白和共伴侣蛋白的新靶点。
IUBMB Life. 2022 Jul;74(7):684-704. doi: 10.1002/iub.2593. Epub 2022 Jan 25.
5
Iron-Sulfur Cluster Complex Assembly in the Mitochondria of .……线粒体中的铁硫簇复合物组装
Plants (Basel). 2020 Sep 9;9(9):1171. doi: 10.3390/plants9091171.
6
Outlining the Complex Pathway of Mammalian Fe-S Cluster Biogenesis.概述哺乳动物 Fe-S 簇生物发生的复杂途径。
Trends Biochem Sci. 2020 May;45(5):411-426. doi: 10.1016/j.tibs.2020.02.001. Epub 2020 Mar 6.
7
Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures.联邦结构模型和数据：整合结构存档研讨会上的成果。
Structure. 2019 Dec 3;27(12):1745-1759. doi: 10.1016/j.str.2019.11.002. Epub 2019 Nov 25.
8
Archiving and disseminating integrative structure models.整合结构模型的归档和传播。
J Biomol NMR. 2019 Jul;73(6-7):385-398. doi: 10.1007/s10858-019-00264-2. Epub 2019 Jul 5.
9
Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.人源 frataxin 结合的铁硫簇组装复合物的结构为其激活机制提供了线索。
Nat Commun. 2019 May 17;10(1):2210. doi: 10.1038/s41467-019-09989-y.
10
NMR as a Tool to Investigate the Processes of Mitochondrial and Cytosolic Iron-Sulfur Cluster Biosynthesis.NMR 作为研究线粒体和细胞质铁硫簇生物合成过程的工具。
Molecules. 2018 Aug 31;23(9):2213. doi: 10.3390/molecules23092213.
本文引用的文献
1
Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly.铁结合的 frataxin 与 ISCU 和铁氧还蛋白在半胱氨酸脱硫酶复合物上的相互作用导致 Fe-S 簇的组装。
J Inorg Biochem. 2018 Jun;183:107-116. doi: 10.1016/j.jinorgbio.2018.03.007. Epub 2018 Mar 15.
2
Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.线粒体 Fe/S 簇合成复合物的结构与功能动态
Nat Commun. 2017 Nov 3;8(1):1287. doi: 10.1038/s41467-017-01497-1.
3
Progress in small-angle scattering from biological solutions at high-brilliance synchrotrons.高亮度同步加速器生物溶液小角散射研究进展
IUCrJ. 2017 Aug 8;4(Pt 5):518-528. doi: 10.1107/S2052252517008740. eCollection 2017 Sep 1.
4
PDB-Dev: a Prototype System for Depositing Integrative/Hybrid Structural Models.PDB-Dev：用于提交整合/混合结构模型的原型系统。
Structure. 2017 Sep 5;25(9):1317-1318. doi: 10.1016/j.str.2017.08.001.
5
: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions.用于大分子溶液小角散射的综合数据分析套件。
J Appl Crystallogr. 2017 Jun 26;50(Pt 4):1212-1225. doi: 10.1107/S1600576717007786. eCollection 2017 Aug 1.
6
Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.人 Fe-S 组装亚基的结构揭示了出乎意料的半胱氨酸脱硫酶结构和酰基-ACP-ISD11 相互作用。
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5325-E5334. doi: 10.1073/pnas.1702849114. Epub 2017 Jun 20.
7
Iron-sulfur cluster biogenesis and trafficking in mitochondria.线粒体中铁硫簇的生物合成与转运
J Biol Chem. 2017 Aug 4;292(31):12754-12763. doi: 10.1074/jbc.R117.787101. Epub 2017 Jun 14.
8
Mitochondrial Cysteine Desulfurase and ISD11 Coexpressed in Escherichia coli Yield Complex Containing Acyl Carrier Protein.线粒体半胱氨酸脱硫酶与ISD11在大肠杆菌中共表达产生含酰基载体蛋白的复合物。
ACS Chem Biol. 2017 Apr 21;12(4):918-921. doi: 10.1021/acschembio.6b01005. Epub 2017 Mar 2.
9
Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis.人类线粒体铁氧化还原蛋白1（FDX1）和铁氧化还原蛋白2（FDX2）均与半胱氨酸脱硫酶结合，并为铁硫簇生物合成提供电子。
Biochemistry. 2017 Jan 24;56(3):487-499. doi: 10.1021/acs.biochem.6b00447. Epub 2017 Jan 11.
10
, a program for rapid shape determination in small-angle scattering.用于小角散射中快速形状测定的一个程序。
J Appl Crystallogr. 2009 Apr 1;42(Pt 2):342-346. doi: 10.1107/S0021889809000338. Epub 2009 Jan 24.
Zotero 插件