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

DOI: 10.1038/s41467-021-26796-6 DOI Help

Authors: Richard W. Meek (University of York) , James N. Blaza (University of York) , Jil A. Busmann (Simon Fraser University) , Matthew G. Alteen (Simon Fraser University) , David J. Vocadlo (Simon Fraser University) , Gideon Davies (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 19832

Open Access Open Access

Abstract: 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.

Journal Keywords: Glycobiology; Transferases

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios III-Titan Krios III at Diamond

Added On: 16/11/2021 19:44

Documents:
s41467-021-26796-6.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Cancer Neurodegenerative Diseases Neurology Non-Communicable Diseases Structural biology

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)