Evidence for a hydrogen sulfide-sensing E3 ligase in yeast.

IF 3.3 3区生物学 Q2 GENETICS & HEREDITY

Genetics Pub Date : 2024-11-06 DOI:10.1093/genetics/iyae154

Zane Johnson, Yun Wang, Benjamin M Sutter, Benjamin P Tu

引用次数: 0

Abstract

In yeast, control of sulfur amino acid metabolism relies upon Met4, a transcription factor that activates the expression of a network of enzymes responsible for the biosynthesis of cysteine and methionine. In times of sulfur abundance, the activity of Met4 is repressed via ubiquitination by the SCFMet30 E3 ubiquitin ligase, but the mechanism by which the F-box protein Met30 senses sulfur status to tune its E3 ligase activity remains unresolved. Herein, we show that Met30 responds to flux through the trans-sulfuration pathway to regulate the MET gene transcriptional program. In particular, Met30 is responsive to the biological gas hydrogen sulfide, which is sufficient to induce ubiquitination of Met4 in vivo. Additionally, we identify important cysteine residues in Met30's WD-40 repeat region that sense the availability of sulfur in the cell. Our findings reveal how SCFMet30 dynamically senses the flow of sulfur metabolites through the trans-sulfuration pathway to regulate the synthesis of these special amino acids.

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酵母中硫化氢感应 E3 连接酶的证据

在酵母中，硫氨基酸代谢的控制依赖于 Met4，它是一种转录因子，能激活负责半胱氨酸和蛋氨酸生物合成的酶网络的表达。在硫丰富的时期，Met4 的活性通过 SCFMet30 E3 泛素连接酶的泛素化被抑制，但 F-box 蛋白 Met30 通过感知硫的状态来调整其 E3 连接酶活性的机制仍未解决。在本文中，我们发现 Met30 可通过反式硫化途径对通量做出反应，从而调节 MET 基因转录程序。特别是，Met30 对生物气体硫化氢有反应，硫化氢足以在体内诱导 Met4 泛素化。此外，我们还在 Met30 的 WD-40 重复区域发现了重要的半胱氨酸残基，这些残基能感知细胞中硫的可用性。我们的发现揭示了 SCFMet30 如何动态地感知硫代谢物通过反式硫化途径的流动，从而调节这些特殊氨基酸的合成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics GENETICS & HEREDITY-

CiteScore

6.90

自引率

6.10%

发文量

177

审稿时长

1.5 months

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.