negative regulation of non-canonical inflammasome complex assembly / glycoprotein metabolic process / protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / protein O-GlcNAc transferase / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / protein O-GlcNAcase ...negative regulation of non-canonical inflammasome complex assembly / glycoprotein metabolic process / protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / protein O-GlcNAc transferase / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / protein O-GlcNAcase / protein deglycosylation / [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity / acetylglucosaminyltransferase activity / glycoprotein catabolic process / regulation of Rac protein signal transduction / regulation of necroptotic process / negative regulation of stem cell population maintenance / protein O-linked glycosylation / NSL complex / regulation of glycolytic process / RIPK1-mediated regulated necrosis / regulation of gluconeogenesis / regulation of synapse assembly / Formation of WDR5-containing histone-modifying complexes / Sin3-type complex / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of stem cell population maintenance / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of proteolysis / hemopoiesis / histone acetyltransferase complex / positive regulation of lipid biosynthetic process / mitophagy / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein ubiquitination / response to nutrient / positive regulation of TORC1 signaling / negative regulation of cell migration / positive regulation of translation / cell projection / 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 / mitochondrial membrane / protein processing / chromatin DNA binding / Regulation of necroptotic cell death / UCH proteinases / HATs acetylate histones / positive regulation of cold-induced thermogenesis / chromatin organization / apoptotic process / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / glutamatergic synapse / 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 / nucleus / membrane / 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.