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Redox requirements for ubiquitin-like urmylation of Ahp1, a 2-Cys peroxiredoxin from yeast.
Redox Biology ( IF 10.7 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.redox.2020.101438
Cindy Brachmann 1 , Lars Kaduhr 1 , André Jüdes 1 , Keerthiraju Ethiraju Ravichandran 2 , James D West 3 , Sebastian Glatt 4 , Raffael Schaffrath 1
Affiliation  

The yeast peroxiredoxin Ahp1, like related anti-oxidant enzymes in other species, undergoes urmylation, a lysine-directed conjugation to ubiquitin-like modifier Urm1. Ahp1 assembles into a homodimer that detoxifies peroxides via forming intersubunit disulfides between peroxidatic and resolving cysteines that are subsequently reduced by the thioredoxin system. Although urmylation coincides with oxidative stress, it is unclear how this modification happens on a molecular level and whether it affects peroxiredoxin activity. Here, we report that thioredoxin mutants decrease Ahp1 urmylation in yeast and each subunit of the oxidized Ahp1 dimer is modified by Urm1 suggesting coupling of urmylation to dimerization. Consistently, Ahp1 mutants unable to form dimers, fail to be urmylated as do mutants that lack the peroxidatic cysteine. Moreover, Ahp1 urmylation involves at least two lysine residues close to the catalytic cysteines and can be prevented in yeast cells exposed to high organic peroxide concentrations. Our results elucidate redox requirements and molecular determinants critical for Ahp1 urmylation, thus providing insights into a potential link between oxidant defense and Urm1 utilization in cells.



中文翻译:

Ahp1 泛素样 urmylation 的氧化还原要求,Ahp1 是一种来自酵母的 2-Cys 过氧化物酶。

酵母过氧化物酶 Ahp1 与其他物种中的相关抗氧化酶一样,会经历 urmylation,这是一种赖氨酸导向的与泛素样修饰剂 Urm1 的结合。Ahp1 组装成同型二聚体,通过在过氧化物和分解半胱氨酸之间形成亚基间二硫化物,随后被硫氧还蛋白系统还原,从而使过氧化物解毒。尽管 urmylation 与氧化应激同时发生,但尚不清楚这种修饰是如何在分子水平上发生的,以及它是否会影响过氧化物酶活性。在这里,我们报告硫氧还蛋白突变体减少酵母中的 Ahp1 urmylation,并且氧化的 Ahp1 二聚体的每个亚基都被 Urm1 修饰,表明 urmylation 与二聚化的耦合。始终如一地,无法形成二聚体的 Ahp1 突变体不能像缺乏过氧化半胱氨酸的突变体一样被尿嘧啶化。而且,Ahp1 urmylation 涉及至少两个靠近催化半胱氨酸的赖氨酸残基,并且可以在暴露于高有机过氧化物浓度的酵母细胞中阻止。我们的结果阐明了氧化还原要求和对 Ahp1 urmylation 至关重要的分子决定因素,从而提供了对细胞中氧化剂防御和 Urm1 利用率之间潜在联系的见解。

更新日期:2020-01-22
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