Motif-dependent binding on the intervening domain regulates O-GlcNAc transferase.
Nat Chem Biol
; 19(11): 1423-1431, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37653170
ABSTRACT
The modification of intracellular proteins with O-linked ß-N-acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. In this study, we identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. Using proteomic peptide phage display (ProP-PD) coupled with structural, biochemical and cellular characterizations, we discovered a strongly enriched peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. We further show that disruption of Int-D binding dysregulates important cellular programs, including response to nutrient deprivation and glucose metabolism. These findings illustrate a mode of OGT substrate recognition and offer key insights into the biological roles of this unique domain.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteins
/
Proteomics
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Chem Biol
Year:
2023
Document type:
Article