Mining for protein S-sulfenylation in uncovers redox-sensitive sites.

TitleMining for protein S-sulfenylation in uncovers redox-sensitive sites.
Publication TypeJournal Article
Year of Publication2019
AuthorsHuang, J., P. Willems, B. Wei, C. Tian, R. B. Ferreira, N. Bodra, S. Agustín M. Gache, K. Wahni, K. Liu, D. Vertommen, K. Gevaert, K. S. Carroll, M. Van Montagu, J. Yang, F. Van Breusegem, and J. Messens
JournalProc Natl Acad Sci U S A
Volume116
Issue42
Pagination21256-21261
Date Published2019 Oct 15
ISSN1091-6490
Abstract

Hydrogen peroxide (HO) is an important messenger molecule for diverse cellular processes. HO oxidizes proteinaceous cysteinyl thiols to sulfenic acid, also known as S-sulfenylation, thereby affecting the protein conformation and functionality. Although many proteins have been identified as S-sulfenylation targets in plants, site-specific mapping and quantification remain largely unexplored. By means of a peptide-centric chemoproteomics approach, we mapped 1,537 S-sulfenylated sites on more than 1,000 proteins in cells. Proteins involved in RNA homeostasis and metabolism were identified as hotspots for S-sulfenylation. Moreover, S-sulfenylation frequently occurred on cysteines located at catalytic sites of enzymes or on cysteines involved in metal binding, hinting at a direct mode of action for redox regulation. Comparison of human and S-sulfenylation datasets provided 155 conserved S-sulfenylated cysteines, including Cys181 of the MITOGEN-ACTIVATED PROTEIN KINASE4 (AtMAPK4) that corresponds to Cys161 in the human MAPK1, which has been identified previously as being S-sulfenylated. We show that, by replacing Cys181 of recombinant AtMAPK4 by a redox-insensitive serine residue, the kinase activity decreased, indicating the importance of this noncatalytic cysteine for the kinase mechanism. Altogether, we quantitatively mapped the S-sulfenylated cysteines in cells under HO stress and thereby generated a comprehensive view on the S-sulfenylation landscape that will facilitate downstream plant redox studies.

DOI10.1073/pnas.1906768116
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID31578252
PubMed Central IDPMC6800386
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