Karasev Dmitry A, Veselova Darya A, Veselovsky Alexander V, Sobolev Boris N, Zgoda Victor G, Archakov Alexander I
Department of Bioinformatics, Institute of Biomedical Chemistry (IBMC), Moscow, Russia.
Department of Biochemistry, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
Proteins. 2018 Jan;86(1):13-20. doi: 10.1002/prot.25397. Epub 2017 Oct 17.
Protein phosphorylation is widely used in biological regulatory processes. The study of spatial features related to phosphorylation sites is necessary to increase the efficacy of recognition of phosphorylation patterns in protein sequences. Using the data on phosphosites found in amino acid sequences, we mapped these sites onto 3D structures and studied the structural variability of the same sites in different PDB entries related to the same proteins. Solvent accessibility was calculated for the residues known to be phosphorylated. A significant change in accessibility was shown for many sites, but several ones were determined as buried in all the structures considered. Most phosphosites were found in coil regions. However, a significant portion was located in the structurally stable ordered regions. Comparison of structures with the same sites in modified and unmodified states showed that the region surrounding a site could be significantly shifted due to phosphorylation. Comparison between non-modified structures (as well as between the modified ones) suggested that phosphorylation stabilizes one of the possible conformations. The local structure around the site could be changed due to phosphorylation, but often the initial conformation of the site surrounding is not altered within bounds of a rather large substructure. In this case, we can observe an extensive displacement within a protein domain. Phosphorylation without structural alteration seems to provide the interface for domain-domain or protein-protein interactions. Accounting for structural features is important for revealing more specific patterns of phosphorylation. It is also necessary for explaining structural changes as a basis for regulatory processes.
蛋白质磷酸化在生物调节过程中被广泛应用。研究与磷酸化位点相关的空间特征对于提高蛋白质序列中磷酸化模式的识别效率是必要的。利用氨基酸序列中发现的磷酸化位点数据，我们将这些位点映射到三维结构上，并研究了与相同蛋白质相关的不同蛋白质数据银行（PDB）条目中相同位点的结构变异性。计算了已知被磷酸化的残基的溶剂可及性。许多位点显示出可及性的显著变化，但有几个位点在所有考虑的结构中都被确定为埋藏状态。大多数磷酸化位点位于卷曲区域。然而，相当一部分位于结构稳定的有序区域。对修饰和未修饰状态下具有相同位点的结构进行比较表明，由于磷酸化，位点周围的区域可能会发生显著移动。未修饰结构之间（以及修饰结构之间）的比较表明，磷酸化使可能的构象之一稳定下来。位点周围的局部结构可能会因磷酸化而改变，但通常位点周围的初始构象在相当大的子结构范围内不会改变。在这种情况下，我们可以观察到蛋白质结构域内的广泛位移。无结构改变的磷酸化似乎为结构域 - 结构域或蛋白质 - 蛋白质相互作用提供了界面。考虑结构特征对于揭示更具体的磷酸化模式很重要。解释结构变化作为调节过程的基础也是必要的。
