دورية أكاديمية
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Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT.

التفاصيل البيبلوغرافية
العنوان: Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT.
المؤلفون: Meek RW; York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK., Blaza JN; York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK. jamie.blaza@york.ac.uk., Busmann JA; Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada., Alteen MG; Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada., Vocadlo DJ; Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.; Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada., Davies GJ; York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK. gideon.davies@york.ac.uk.
المصدر: Nature communications [Nat Commun] 2021 Nov 11; Vol. 12 (1), pp. 6508. Date of Electronic Publication: 2021 Nov 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Amino Acids/*metabolism , Chromium/*metabolism , Cryoelectron Microscopy/*methods , Nicotinic Acids/*metabolism, Amino Acids/chemistry ; Chromium/chemistry ; Crystallography, X-Ray ; Glycomics ; Mutation/genetics ; Nicotinic Acids/chemistry ; Protein Structure, Secondary
مستخلص: 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.
(© 2021. The Author(s).)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MR/T040742/1 United Kingdom MRC_ Medical Research Council; United Kingdom BB_ Biotechnology and Biological Sciences Research Council
المشرفين على المادة: 0 (Amino Acids)
0 (Nicotinic Acids)
0 (glucose tolerance factor)
0R0008Q3JB (Chromium)
تواريخ الأحداث: Date Created: 20211112 Date Completed: 20211224 Latest Revision: 20240508
رمز التحديث: 20240508
مُعرف محوري في PubMed: PMC8586251
DOI: 10.1038/s41467-021-26796-6
PMID: 34764280
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-26796-6