protein N-acetylglucosaminyltransferase complex / protein O-GlcNAc transferase / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / positive regulation of transcription from RNA polymerase II promoter by glucose / acetylglucosaminyltransferase activity / regulation of necroptotic process / regulation of Rac protein signal transduction / negative regulation of stem cell population maintenance / protein O-linked glycosylation ...protein N-acetylglucosaminyltransferase complex / protein O-GlcNAc transferase / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / positive regulation of transcription from RNA polymerase II promoter by glucose / acetylglucosaminyltransferase activity / regulation of necroptotic process / regulation of Rac protein signal transduction / negative regulation of stem cell population maintenance / protein O-linked glycosylation / 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 / 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 / nucleus / plasma membrane / cytosol 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2021 タイトル: Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT. 著者: Richard W Meek / James N Blaza / Jil A Busmann / Matthew G Alteen / David J Vocadlo / Gideon J Davies / 要旨: The O-linked β-N-acetylglucosamine modification is a core signalling mechanism, with erroneous patterns leading to cancer and neurodegeneration. Although thousands of proteins are subject to this ...The O-linked β-N-acetylglucosamine modification is a core signalling mechanism, with erroneous patterns leading to cancer and neurodegeneration. Although thousands of proteins are subject to this modification, only a single essential glycosyltransferase catalyses its installation, the O-GlcNAc transferase, OGT. Previous studies have provided truncated structures of OGT through X-ray crystallography, but the full-length protein has never been observed. Here, we report a 5.3 Å cryo-EM model of OGT. We show OGT is a dimer, providing a structural basis for how some X-linked intellectual disability mutations at the interface may contribute to disease. We observe that the catalytic section of OGT abuts a 13.5 tetratricopeptide repeat unit region and find the relative positioning of these sections deviate from the previously proposed, X-ray crystallography-based model. We also note that OGT exhibits considerable heterogeneity in tetratricopeptide repeat units N-terminal to the dimer interface with repercussions for how OGT binds protein ligands and partners.