Moldovan Mikhail, Gelfand Mikhail S
Skolkovo Institute of Science and Technology, Moscow, Russia.
A. A. Kharkevich Institute for Information Transmission Problems, Moscow, Russia.
PeerJ. 2020 Dec 2;8:e10436. doi: 10.7717/peerj.10436. eCollection 2020.
Protein phosphorylation is the best studied post-translational modification strongly influencing protein function. Phosphorylated amino acids not only differ in physico-chemical properties from non-phosphorylated counterparts, but also exhibit different evolutionary patterns, tending to mutate to and originate from negatively charged amino acids (NCAs). The distribution of phosphosites along protein sequences is non-uniform, as phosphosites tend to cluster, forming so-called phospho-islands.
Here, we have developed a hidden Markov model-based procedure for the identification of phospho-islands and studied the properties of the obtained phosphorylation clusters. To check robustness of evolutionary analysis, we consider different models for the reconstructions of ancestral phosphorylation states.
Clustered phosphosites differ from individual phosphosites in several functional and evolutionary aspects including underrepresentation of phosphotyrosines, higher conservation, more frequent mutations to NCAs. The spectrum of tissues, frequencies of specific phosphorylation contexts, and mutational patterns observed near clustered sites also are different.
蛋白质磷酸化是研究最为深入的翻译后修饰，对蛋白质功能有强烈影响。磷酸化氨基酸不仅在物理化学性质上与未磷酸化的对应物不同，而且呈现出不同的进化模式，倾向于突变为带负电荷的氨基酸（NCA）并由其产生。磷酸化位点沿蛋白质序列的分布并不均匀，因为磷酸化位点倾向于聚集，形成所谓的磷酸化岛。
在此，我们开发了一种基于隐马尔可夫模型的程序来识别磷酸化岛，并研究所得磷酸化簇的特性。为检验进化分析的稳健性，我们考虑了用于重建祖先磷酸化状态的不同模型。
成簇的磷酸化位点在几个功能和进化方面与单个磷酸化位点不同，包括磷酸酪氨酸的代表性不足、更高的保守性、更频繁地突变为带负电荷的氨基酸。在成簇位点附近观察到的组织谱、特定磷酸化背景的频率和突变模式也有所不同。
