Laboratory of Biochemistry, Wageningen University, Stippeneng 4, 6708WE, Wageningen, the Netherlands.
Sci Rep. 2020 Mar 2;10(1):3797. doi: 10.1038/s41598-020-60733-9.
Protein oligomerization is a fundamental process to build complex functional modules. Domains that facilitate the oligomerization process are diverse and widespread in nature across all kingdoms of life. One such domain is the Phox and Bem1 (PB1) domain, which is functionally well-studied in the animal kingdom. However, beyond animals, neither the origin nor the evolutionary patterns of PB1-containing proteins are understood. While PB1 domain proteins have been found in other kingdoms including plants, it is unclear how these relate to animal PB1 proteins. To address this question, we utilized large transcriptome datasets along with the proteomes of a broad range of species. We discovered eight PB1 domain-containing protein families in plants, along with four each in Protozoa and Fungi and three families in Chromista. Studying the deep evolutionary history of PB1 domains throughout eukaryotes revealed the presence of at least two, but likely three, ancestral PB1 copies in the Last Eukaryotic Common Ancestor (LECA). These three ancestral copies gave rise to multiple orthologues later in evolution. Analyzing the sequence and secondary structure properties of plant PB1 domains from all the eight families showed their common ubiquitin β-grasp fold, despite poor sequence identity. Tertiary structural models of these plant PB1 families, combined with Random Forest based classification, indicated family-specific differences attributed to the length of PB1 domain and the proportion of β-sheets. Thus, this study not only identifies novel PB1 families, but also provides an evolutionary basis to understand their diverse functional interactions.
蛋白质寡聚化是构建复杂功能模块的基础过程。促进寡聚化过程的结构域在生命的所有领域中都是多种多样且广泛存在的。这样的结构域之一是 Phox 和 Bem1（PB1）结构域，它在动物王国中的功能研究得很好。然而，除了动物之外，PB1 结构域蛋白的起源和进化模式都不清楚。虽然在包括植物在内的其他生物中已经发现了 PB1 结构域蛋白，但尚不清楚这些蛋白与动物 PB1 蛋白有何关系。为了解决这个问题，我们利用了大量转录组数据集以及广泛物种的蛋白质组。我们在植物中发现了八个含有 PB1 结构域的蛋白家族，原生动物和真菌中各有四个，Chromista 中有三个。研究真核生物中 PB1 结构域的深层进化历史表明，在最后的真核共同祖先（LECA）中至少存在两个，但可能是三个，祖先 PB1 拷贝。这三个祖先拷贝在后来的进化中产生了多个直系同源物。分析所有八个家族的植物 PB1 结构域的序列和二级结构特性表明，尽管序列同一性较差，但它们都具有共同的泛素 β 把握折叠。这些植物 PB1 家族的三级结构模型，结合基于随机森林的分类，表明了家族特异性的差异归因于 PB1 结构域的长度和 β-折叠的比例。因此，这项研究不仅确定了新的 PB1 家族，而且还为理解它们多样化的功能相互作用提供了进化基础。
