Recognition of a Glycosylation Substrate by the O-GlcNAc Transferase TPR Repeats

Overview

Journal Open Biol

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Jun 30

PMID 28659383

Citations 30

Authors

Karim Rafie

Olawale Raimi

Andrew T Ferenbach

Vladimir S Borodkin

Vaibhav Kapuria

Daan M F van Aalten

Affiliations

Soon will be listed here.

Abstract

O-linked -acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site.

Citing Articles

Photoactivatable O-GlcNAc Transferase Library Enables Covalent Chemical Capture of Solvent-Exposed TPR Domain Interactions.

Joiner C, Glogowski T, NewRingeisen E, Huynh H, Roberts M, Rognerud M Chembiochem. 2024; 26(1):e202400709.

PMID: 39541256 PMC: 11729469. DOI: 10.1002/cbic.202400709.

Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.

Ma B, Khan K, Xu T, Xeque Amada J, Guo Z, Huang Y J Am Chem Soc. 2024; 146(14):9779-9789.

PMID: 38561350 PMC: 11009946. DOI: 10.1021/jacs.3c14380.

Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex.

Lu P, Liu Y, He M, Cao T, Yang M, Qi S Nat Commun. 2023; 14(1):6952.

PMID: 37907462 PMC: 10618255. DOI: 10.1038/s41467-023-42427-8.

An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal.

Omelkova M, Fenger C, Murray M, Hammer T, Pravata V, Galan Bartual S Dis Model Mech. 2023; 16(6).

PMID: 37334838 PMC: 10309585. DOI: 10.1242/dmm.049132.

Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY.

Kumar S, Wang Y, Zhou Y, Dillard L, Li F, Sciandra C Nat Commun. 2023; 14(1):1538.

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