School of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
School of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Cell Rep. 2023 Jul 25;42(7):112796. doi: 10.1016/j.celrep.2023.112796. Epub 2023 Jul 14.
The subcellular localization of proteins is critical for their functions in eukaryotic cells and is tightly correlated with protein modifications. Here, we comprehensively investigate the nuclear-cytoplasmic distributions of the phosphorylated, O-GlcNAcylated, and non-modified forms of proteins to dissect the correlation between protein distribution and modifications. Phosphorylated and O-GlcNAcylated proteins have overall higher nuclear distributions than non-modified ones. Different distributions among the phosphorylated, O-GlcNAcylated, and non-modified forms of proteins are associated with protein size, structure, and function, as well as local environment and adjacent residues around modification sites. Moreover, we perform site-mutagenesis experiments using phosphomimetic and phospho-null mutants of two proteins to validate the proteomic results. Additionally, the effects of the OGT/OGA inhibition on glycoprotein distribution are systematically investigated, and the distribution changes of glycoproteins are related to their abundance changes under the inhibitions. Systematic investigation of the relationship between protein modification and localization advances our understanding of protein functions.
蛋白质的亚细胞定位对于其在真核细胞中的功能至关重要，并且与蛋白质修饰紧密相关。在这里，我们全面研究了磷酸化、O-GlcNAc 化和非修饰形式的蛋白质的核质分布，以剖析蛋白质分布与修饰之间的相关性。磷酸化和 O-GlcNAc 化的蛋白质总体上比非修饰的蛋白质具有更高的核分布。磷酸化、O-GlcNAc 化和非修饰形式的蛋白质之间的不同分布与蛋白质大小、结构和功能以及局部环境和修饰位点附近的相邻残基有关。此外，我们使用两种蛋白质的磷酸化模拟和磷酸化缺失突变体进行了位点诱变实验，以验证蛋白质组学结果。此外，还系统研究了 OGT/OGA 抑制对糖蛋白分布的影响，并且在抑制下糖蛋白的分布变化与它们的丰度变化有关。对蛋白质修饰和定位之间关系的系统研究增进了我们对蛋白质功能的理解。
