An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase.
Sci Adv
; 10(9): eadj8829, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38416819
ABSTRACT
N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (α, ß, and γ), where α and ß can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown. Here, we show that both α and ß in GalNAc-T1 uniquely orchestrate the O-glycosylation of various glycopeptide substrates. The α repeat directs O-glycosylation to acceptor sites carboxyl-terminal to an existing GalNAc, while the ß repeat directs O-glycosylation to amino-terminal sites. In addition, GalNAc-T1 incorporates α and ß into various substrate binding modes to cooperatively increase the specificity toward an acceptor site located between two existing O-glycans. Our studies highlight a unique mechanism by which dual lectin repeats expand substrate specificity and provide crucial information for identifying the biological substrates of GalNAc-T1.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
N-Acetylgalactosaminyltransferases
/
Mucins
Language:
En
Journal:
Sci Adv
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos