|Title||Mining for protein S-sulfenylation in uncovers redox-sensitive sites.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Huang, 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|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2019 Oct 15|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC6800386|
Mining for protein S-sulfenylation in uncovers redox-sensitive sites.