Atypical structural tendencies among low-complexity domains in the protein data bank proteome
Atypical structural tendencies among low-complexity domains in the protein data bank proteome
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DOI：
10.1371/journal.pcbi.1007487
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发表时间：
2020-01-01
影响因子：
4.3
通讯作者：
Ross, Eric D.
中科院分区：
文献类型：
--
作者：
Cascarina, Sean M.;Elder, Mikaela R.;Ross, Eric D.
各种研究表明，低复杂性结构域 (LCD) 本质上往往是无序的，并且在蛋白质数据库 (PDB) 的结构化蛋白质中相对罕见。尽管液晶显示器通常被视为单一类别，但我们之前发现富含不同氨基酸的液晶显示器在蛋白质代谢和功能方面可以表现出显着差异。因此，我们想知道 LCD 的结构构象是否同样取决于每个 LCD 中富集的特定氨基酸。在这里，我们直接检查了整个 PDB 蛋白质组中单个氨基酸的富集和二级结构趋势之间的关系。二级结构趋势随着富集氨基酸的特性及其富集程度而变化。此外，富含物理化学相似氨基酸（例如缬氨酸与亮氨酸）的 LCD 的二级结构谱经常出现差异，这表明由相关氨基酸组成的 LCD 可能具有不同的二级结构倾向。 LCD二级结构倾向与许多预先存在的二级结构倾向量表的比较导致某些类型的LCD的相关性相对较差，这表明随着序列复杂性降低，这些量表可能无法捕获二级结构倾向。总的来说，这些观察结果提供了通过单个氨基酸富集的性质和程度解析的 LCD 结构趋势的高度解析视图。作者摘要 蛋白质采用的结构与其氨基酸序列直接相关。蛋白质序列中的低复杂性结构域 (LCD) 是仅由几种不同类型的氨基酸组成的不寻常区域。尽管这是将序列分类为 LCD 的关键特征，但 LCD 的物理特性将根据每个结构域中发现的氨基酸类型而有所不同。例如，序列“AAAAAAAAAA”、“EEEEEEEEEE”和“EEKRKEEEKE”将具有非常不同的属性，即使它们都按传统方法分类为 LCD。在之前的一项研究中，我们开发了一种新方法，可以将 LCD 进一步划分为更能反映其物理特性差异的类别。在这项研究中，我们应用这种方法来检查液晶显示器的结构，当液晶显示器根据氨基酸分为不同类别时。这使我们能够定义 LCD 中氨基酸类型及其相应结构之间的关系。由于蛋白质结构与蛋白质功能密切相关，这对于了解多种蛋白质中LCD的基本功能和性质具有重要意义。
A variety of studies have suggested that low-complexity domains (LCDs) tend to be intrinsically disordered and are relatively rare within structured proteins in the protein data bank (PDB). Although LCDs are often treated as a single class, we previously found that LCDs enriched in different amino acids can exhibit substantial differences in protein metabolism and function. Therefore, we wondered whether the structural conformations of LCDs are likewise dependent on which specific amino acids are enriched within each LCD. Here, we directly examined relationships between enrichment of individual amino acids and secondary structure tendencies across the entire PDB proteome. Secondary structure tendencies varied as a function of the identity of the amino acid enriched and its degree of enrichment. Furthermore, divergence in secondary structure profiles often occurred for LCDs enriched in physicochemically similar amino acids (e.g. valine vs. leucine), indicating that LCDs composed of related amino acids can have distinct secondary structure tendencies. Comparison of LCD secondary structure tendencies with numerous pre-existing secondary structure propensity scales resulted in relatively poor correlations for certain types of LCDs, indicating that these scales may not capture secondary structure tendencies as sequence complexity decreases. Collectively, these observations provide a highly resolved view of structural tendencies among LCDs parsed by the nature and magnitude of single amino acid enrichment.Author summary The structures that proteins adopt are directly related to their amino acid sequences. Low-complexity domains (LCDs) in protein sequences are unusual regions made up of only a few different types of amino acids. Although this is the key feature that classifies sequences as LCDs, the physical properties of LCDs will differ based on the types of amino acids that are found in each domain. For example, the sequences "AAAAAAAAAA", "EEEEEEEEEE", and "EEKRKEEEKE" will have very different properties, even though they would all be classified as LCDs by traditional methods. In a previous study, we developed a new method to further divide LCDs into categories that more closely reflect the differences in their physical properties. In this study, we apply that approach to examine the structures of LCDs when sorted into different categories based on their amino acids. This allowed us to define relationships between the types of amino acids in the LCDs and their corresponding structures. Since protein structure is closely related to protein function, this has important implications for understanding the basic functions and properties of LCDs in a variety of proteins.