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Meek RW, Blaza JN, Busmann JA, et al. Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT. Nat Commun. 2021;12(1):6508doi: 10.1038/s41467-021-26796-6.
Meek, R. W., Blaza, J. N., Busmann, J. A., Alteen, M. G., Vocadlo, D. J., & Davies, G. J. (2021). Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT. Nature communications, 12(1), 6508. https://doi.org/10.1038/s41467-021-26796-6
Meek, Richard W, et al. "Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT." Nature communications vol. 12,1 (2021): 6508. doi: https://doi.org/10.1038/s41467-021-26796-6
Meek RW, Blaza JN, Busmann JA, Alteen MG, Vocadlo DJ, Davies GJ. Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT. Nat Commun. 2021 Nov 11;12(1):6508. doi: 10.1038/s41467-021-26796-6. PMID: 34764280; PMCID: PMC8586251.
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Nat Commun. 2021 Nov 11;12(1):6508. doi: 10.1038/s41467-021-26796-6.

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

Nature communications

Richard W Meek, James N Blaza, Jil A Busmann, Matthew G Alteen, David J Vocadlo, Gideon J Davies

Affiliations

  1. York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK.
  2. York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK. [email protected].
  3. Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.
  4. Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.
  5. York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, UK. [email protected].

PMID: 34764280 PMCID: PMC8586251 DOI: 10.1038/s41467-021-26796-6

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.

© 2021. The Author(s).

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