Kamacioglu Altug, Tuncbag Nurcan, Ozlu Nurhan
Department of Molecular Biology and Genetics, Koc University, Istanbul, Turkey.
Chemical and Biological Engineering, College of Engineering, Koc University, 34450 Istanbul, Turkey; School of Medicine, Koc University, 34450 Istanbul, Turkey; Koc University Research Center for Translational Medicine (KUTTAM), 34450 Istanbul, Turkey.
Structure. 2021 Nov 4;29(11):1219-1229.e3. doi: 10.1016/j.str.2021.06.008. Epub 2021 Jun 29.
Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, protein structures add another layer of information about their functionality. In this study, we systematically characterize phospho-sites based on their 3D locations in the protein and establish a location map for phospho-sites. More than 250,000 phospho-sites have been analyzed, of which 8,686 sites match at least one structure and are stratified based on their respective 3D positions. Core phospho-sites possess two distinct groups based on their dynamicity. Dynamic core phosphorylations are significantly more functional compared with static ones. The dynamic core and the interface phospho-sites are the most functional among all 3D phosphorylation groups. Our analysis provides global characterization and stratification of phospho-sites from a structural perspective that can be utilized for predicting functional relevance and filtering out false positives in phosphoproteomic studies.
磷酸化是几乎所有细胞过程中必不可少的翻译后修饰。多项全局磷酸蛋白质组学分析揭示了不同条件下的磷酸化谱。除了磷酸化位点的鉴定，蛋白质结构还为其功能增添了另一层信息。在本研究中，我们基于磷酸化位点在蛋白质中的三维位置对其进行系统表征，并建立了磷酸化位点的位置图谱。我们分析了超过25万个磷酸化位点，其中8686个位点与至少一种结构匹配，并根据其各自的三维位置进行了分层。核心磷酸化位点根据其动态性可分为两个不同的组。与静态磷酸化相比，动态核心磷酸化具有更显著的功能。在所有三维磷酸化组中，动态核心和界面磷酸化位点功能最为显著。我们的分析从结构角度对磷酸化位点进行了全局表征和分层，可用于预测功能相关性并在磷酸蛋白质组学研究中筛选假阳性结果。
