Faculty of Biology, Johannes Gutenberg University, Biozentrum I, Hans-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany.
Bioinformatics Research Group, Department of Biochemistry, ELTE Eötvös Loránd University, MTA-ELTE Momentum, H-1117 Budapest, Hungary.
Biomolecules. 2020 Oct 6;10(10):1413. doi: 10.3390/biom10101413.
Intrinsically disordered proteins (IDPs) contain regions lacking intrinsic globular structure (intrinsically disordered regions, IDRs). IDPs are present across the tree of life, with great variability of IDR type and frequency even between closely related taxa. To investigate the function of IDRs, we evaluated and compared the distribution of disorder content in 10,695 reference proteomes, confirming its high variability and finding certain correlation along the Euteleostomi (bony vertebrates) lineage to number of cell types. We used the comparison of orthologs to study the function of disorder related to increase in cell types, observing that multiple interacting subunits of protein complexes might gain IDRs in evolution, thus stressing the function of IDRs in modulating protein-protein interactions, particularly in the cell nucleus. Interestingly, the conservation of local compositional biases of IDPs follows residue-type specific patterns, with E- and K-rich regions being evolutionarily stable and Q- and A-rich regions being more dynamic. We provide a framework for targeted evolutionary studies of the emergence of IDRs. We believe that, given the large variability of IDR distributions in different species, studies using this evolutionary perspective are required.
无规卷曲蛋白质（IDPs）包含缺乏固有球状结构的区域（无规卷曲区域，IDRs）。IDPs 存在于生命之树的各个分支中，即使在密切相关的分类群之间，IDR 类型和频率也存在很大的可变性。为了研究 IDRs 的功能，我们评估并比较了 10695 个参考蛋白质组中无序含量的分布，证实了其高度的可变性，并发现沿真骨鱼（硬骨脊椎动物）谱系到细胞类型数量存在一定的相关性。我们使用同源物的比较来研究与细胞类型增加相关的无序功能，观察到蛋白质复合物的多个相互作用亚基可能在进化过程中获得 IDRs，从而强调 IDRs 在调节蛋白质-蛋白质相互作用中的功能，特别是在细胞核中。有趣的是，无规卷曲蛋白质局部组成偏性的保守性遵循残基类型特异性模式，富含 E 和 K 的区域具有进化稳定性，富含 Q 和 A 的区域则更具动态性。我们为 IDRs 出现的有针对性的进化研究提供了一个框架。我们认为，鉴于不同物种中 IDR 分布的巨大可变性，需要使用这种进化视角进行研究。
