UMR 7365 CNRS-Université de Lorraine IMoPA, Biopôle, Campus Biologie-Santé, Vandœuvre-lès-Nancy, France.
Institute for Integrative Biology of the Cell (I2BC), CNRS, CEA-Saclay, Université Paris-Saclay, iBiTecS/SBIGEM, Laboratoire Stress Oxydant et Cancer, Gif-sur-Yvette, France.
Nat Chem Biol. 2017 Aug;13(8):909-915. doi: 10.1038/nchembio.2412. Epub 2017 Jun 19.
In Saccharomyces cerevisiae, Yap1 regulates an HO-inducible transcriptional response that controls cellular HO homeostasis. HO activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with HO, 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.
在酿酒酵母中， Yap1 调节 HO 诱导的转录反应，控制细胞内 HO 稳态。HO 通过中间的硫氧还蛋白 Orp1 通过氧化作用激活 yap1。与 HO 反应后，Orp1 催化半胱氨酸氧化生成亚磺酸，然后与 yap1 形成分子间二硫键，导致 yap1 激活，或形成分子内二硫键，使酶进入其过氧酶循环。以前不知道这两个竞争反应中的第一个反应（动力学上不利）是如何发生的。我们表明， Yap1 结合蛋白 Ybp1 将 Orp1 和 yap1 聚集在一起形成三元复合物，该复合物选择性地激活 Orp1 亚磺酰化半胱氨酸与六个 yap1 半胱氨酸之一的缩合，同时抑制 Orp1 分子内二硫键形成。我们提出 Ybp1 作为支架蛋白和亚磺酸伴侣蛋白发挥作用，以提供通过反应性亚磺酸物种转移氧化还原当量的特异性。
