protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / protein O-GlcNAc transferase / glycoprotein metabolic process / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / glycoprotein catabolic process / protein O-GlcNAcase ...protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / protein O-GlcNAc transferase / glycoprotein metabolic process / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / glycoprotein catabolic process / protein O-GlcNAcase / : / : / [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity / acetylglucosaminyltransferase activity / regulation of necroptotic process / regulation of Rac protein signal transduction / negative regulation of stem cell population maintenance / protein O-linked glycosylation / protein deglycosylation / NSL complex / regulation of glycolytic process / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / RIPK1-mediated regulated necrosis / regulation of synapse assembly / regulation of gluconeogenesis / positive regulation of stem cell population maintenance / Formation of WDR5-containing histone-modifying complexes / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of proteolysis / mitophagy / hemopoiesis / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / histone acetyltransferase complex / positive regulation of lipid biosynthetic process / negative regulation of protein ubiquitination / positive regulation of TORC1 signaling / negative regulation of cell migration / response to nutrient / cell projection / positive regulation of translation / mitochondrial membrane / beta-N-acetylglucosaminidase activity / cellular response to glucose stimulus / negative regulation of transforming growth factor beta receptor signaling pathway / circadian regulation of gene expression / response to insulin / Regulation of necroptotic cell death / protein processing / chromatin DNA binding / UCH proteinases / chromatin organization / positive regulation of cold-induced thermogenesis / HATs acetylate histones / glutamatergic synapse / apoptotic process / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytosol 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
32130053
中国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex. 著者: Ping Lu / Yusong Liu / Maozhou He / Ting Cao / Mengquan Yang / Shutao Qi / Hongtao Yu / Haishan Gao / 要旨: O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins. In response to nutritional and hormonal signals, O- ...O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins. In response to nutritional and hormonal signals, O-GlcNAcylation regulates diverse cellular processes by modulating the stability, structure, and function of target proteins. Dysregulation of O-GlcNAcylation has been implicated in the pathogenesis of cancer, diabetes, and neurodegeneration. A single pair of enzymes, the O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), catalyzes the addition and removal of O-GlcNAc on over 3,000 proteins in the human proteome. However, how OGT selects its native substrates and maintains the homeostatic control of O-GlcNAcylation of so many substrates against OGA is not fully understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of human OGT and the OGT-OGA complex. Our studies reveal that OGT forms a functionally important scissor-shaped dimer. Within the OGT-OGA complex structure, a long flexible OGA segment occupies the extended substrate-binding groove of OGT and positions a serine for O-GlcNAcylation, thus preventing OGT from modifying other substrates. Conversely, OGT disrupts the functional dimerization of OGA and occludes its active site, resulting in the blocking of access by other substrates. This mutual inhibition between OGT and OGA may limit the futile O-GlcNAcylation cycles and help to maintain O-GlcNAc homeostasis.