Physiological relevance of peroxiredoxin hetero-oligomerisation

过氧化物酶是原核生物和真核生物中最丰富的蛋白质的前1-10%。它们是（i）氢过氧化物解毒的中心，也可以（ii）作为信号转导中的过氧化物传感器和（iii）在热和/或氧化应激期间作为伴侣。这三种不同的生理功能耦合到一个高度灵活的四级结构，范围从同源二聚体和十聚体到1.0 MDa低聚物。令人惊讶的是，大多数真核生物有两个或甚至三个明显多余的胞质过氧化物酶同工型。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酶Tsa 1和Tsa 2很容易形成异源寡聚体。因此，我们提出，peroxiredoxin冗余不是一个巧合，而是peroxiredoxin异源寡聚化是一种机制，服务于大大扩展这个蛋白质家族的功能可塑性。尽管PubMed检索显示超过5000篇关于过氧化物酶的出版物，但据我们所知，只有两项研究涉及酵母和人类细胞系中过氧化物酶异源寡聚体的生理形成。迄今为止，过氧化物氧还蛋白异源寡聚化的生理相关性尚不清楚。在本项目中，我们要分析是否peroxiredoxins可以真正被视为孤立的实体或是否peroxiredoxin异源寡聚体作为催化和调节整合枢纽，链接的分子可塑性和功能多样性的peroxiredoxins。

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.