Physiological relevance of peroxiredoxin hetero-oligomerisation

过氧化还原蛋白异源寡聚化的生理相关性

• 批准号: 508372800
• 负责人: Professor Dr. Marcel Deponte
• 金额: --
• 依托单位: Lehrstuhl für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/508372800?language=en
• 关键词: Physiological; relevance; peroxiredoxin; hetero; oligomerisation

Peroxiredoxins are among the top 1-10% of most abundant proteins in pro- and eukaryotes. They are central for (i) hydroperoxide detoxification and can also act (ii) as peroxide sensors in signal transduction and (iii) as chaperones during heat and/or oxidative stress. These three different physiological functions are coupled to a highly flexible quaternary structure that ranges from homo-dimers and -decamers to 1.0 MDa oligomers. Surprisingly, most eukaryotes have two or even three apparently redundant cytosolic peroxiredoxin isoforms. Although considered almost exclusively as independent entities, intriguingly we recently observed that the peroxiredoxins Tsa1 and Tsa2 from baker’s yeast readily form hetero-oligomers. We thus propose that peroxiredoxin redundancy is not a coincidence but rather that peroxiredoxin hetero-oligomerization is a mechanism that serves to greatly expand the functional plasticity of this protein family. Even though PubMed searches reveal more than 5000 publications on peroxiredoxins, there are, to the best of our knowledge, only two studies that have addressed the physiological formation of peroxiredoxin hetero-oligomers in yeast and in human cell lines. The physiological relevance of peroxiredoxin hetero-oligomerization is unknown to date. In the present project, we want to analyze whether peroxiredoxins can be really regarded as isolated entities or whether peroxiredoxin hetero-oligomers act as catalytic and modulatory integration hubs that link the molecular plasticity and functional versatility of peroxiredoxins.

过氧化物还毒素是原核和真核生物中含量最高的1-10%的蛋白质之一。它们是(i)氢过氧化物解毒的核心，也可以作为（ii）信号转导中的过氧化物传感器和（iii）在热应激和/或氧化应激中作为伴侣。这三种不同的生理功能与高度灵活的四元结构相结合，其范围从同型二聚体和-十聚体到1.0 MDa低聚物。令人惊讶的是，大多数真核生物有两个甚至三个明显冗余的细胞质过氧化物还毒素同工型。虽然几乎完全被认为是独立的实体，但有趣的是，我们最近观察到面包酵母中的过氧化物还毒素Tsa1和Tsa2很容易形成异聚低聚物。因此，我们提出过氧还蛋白冗余不是巧合，而是过氧还蛋白异寡聚化是一种机制，有助于极大地扩大该蛋白家族的功能可塑性。尽管PubMed检索了5000多篇关于过氧化物还毒素的出版物，但据我们所知，只有两篇研究涉及酵母和人类细胞系中过氧化物还毒素异聚物的生理形成。迄今为止，过氧化物还蛋白异寡聚的生理相关性尚不清楚。在本项目中，我们想分析过氧化物还毒素是否真的可以被视为孤立的实体，或者过氧化物还毒素异质低聚物是否作为催化和调节的整合中心，将过氧化物还毒素的分子可塑性和功能多功能性联系起来。