Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

被引：202

作者：

Akter, Salma ^{[1
]}

Fu, Ling ^{[2
,3
,4
]}

Jung, Youngeun ^{[1
]}

Lo Conte, Mauro ^{[1
,7
]}

Lawson, J. Reed ^{[5
,6
]}

Lowther, W. Todd ^{[5
,6
]}

Sun, Rui ^{[2
,3
,4
]}

Liu, Keke ^{[2
,3
,4
]}

Yang, Jing ^{[2
,3
,4
]}

Carroll, Kate S. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA

[2] Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China

[3] Natl Ctr Prot Sci Beijing, Beijing, Peoples R China

[4] Beijing Inst Life, Beijing, Peoples R China

[5] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA

[6] Wake Forest Sch Med, Struct Biol Ctr, Winston Salem, NC USA

[7] Novo Nordisk Res Ctr, Seattle, WA USA

来源：

NATURE CHEMICAL BIOLOGY | 2018年 / 14卷 / 11期

基金：

中国国家自然科学基金; 国家重点研发计划; 美国国家卫生研究院;

关键词：

ACTIVE-SITE CYSTEINE; PROTEIN IDENTIFICATION; HYDROGEN-PEROXIDE; SULFIREDOXIN; OXIDATION; PEROXIREDOXIN; CANCER; CHEMISTRY; SYSTEM; CELLS;

D O I：

10.1038/s41589-018-0116-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.

引用

页码：995 / +

页数：13

共 59 条

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Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2 [J].