A scaffold protein that chaperones a cysteine-sulfenic acid in H2O2 signaling

• Published in: Nature chemical biology Vol. 13; no. 8; pp. 909 - 915
• Main Authors: Bersweiler, Antoine, D'Autréaux, Benoît, Mazon, Hortense, Kriznik, Alexandre, Belli, Gemma, Delaunay-Moisan, Agnès, Toledano, Michel B, Rahuel-Clermont, Sophie
• Format: Journal Article
• Language: English
• Published: Cambridge Nature Publishing Group 01.08.2017
• Subjects: Acids; Bacteria; Biochemistry, Molecular Biology; Catalysis; Chaperones; Cysteine; Fungi; Homeostasis; Hydrogen peroxide; Life Sciences; Oxidation; Peroxidase; Proteins; Saccharomyces cerevisiae; Signal transduction; Sulfenic acid; Thiol peroxidase; Transcription; Yes-associated protein
• ISSN: 1552-4450; 1552-4469
• DOI: 10.1038/nchembio.2412

In Saccharomyces cerevisiae, Yap1 regulates an H2 O2 -inducible transcriptional response that controls cellular H2 O2 homeostasis. H2 O2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H2 O2 , Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown. We show that the Yap1-binding protein Ybp1 brings together Orp1 and Yap1 into a ternary complex that selectively activates condensation of the Orp1 sulfenylated cysteine with one of the six Yap1 cysteines while inhibiting Orp1 intramolecular disulfide formation. We propose that Ybp1 operates as a scaffold protein and as a sulfenic acid chaperone to provide specificity in the transfer of oxidizing equivalents by a reactive sulfenic acid species.