PXD047845

PXD047845 is an original dataset announced via ProteomeXchange.

Title	An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase
Description	N-acetylgalactosaminyl transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex post-translational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a C-terminal lectin domain consisting of three homologous repeats (, , where  and can potentially interact with O-GalNAc on substrates to enhance activity towards a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates diverse biological functions, including heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown. Here, we show that both  and  in GalNAc-T1 uniquely orchestrate the O-glycosylation of various glycopeptide substrates. The repeat directs O-glycosylation to acceptor sites C-terminal to an existing GalNAc, while the repeat directs O-glycosylation to N-terminal sites. Additionally, GalNAc-T1 incorporates  and  binding into various substrate binding modes to cooperatively increase the specificity towards an intermediate acceptor site. Our studies highlight a unique mechanism by which dual lectin repeats expand substrate specificity and inform on identifying the biological substrates affected by disruptions in GalNAc-T1 function.
HostingRepository	PRIDE
AnnounceDate	2024-05-23
AnnouncementXML	Submission_2024-05-22_23:44:49.463.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weiming Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	O-(N-acetylamino)galactosyl-L-threonine; O-(N-acetylamino)galactosyl-L-serine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-14 21:09:02	ID requested
⏵ 1	2024-05-22 23:44:50	announced

10.1126/sciadv.adj8829;

Collette AM, Hassan SA, Schmidt SI, Lara AJ, Yang W, Samara NL, An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase. Sci Adv, 10(9):eadj8829(2024) [pubmed]

submitter keyword: MUC1, O-glycosylation, structure, lectin domain, substrate specificity

Nadine L. Samara
contact affiliation	Structural Biochemistry Unit, NIDCR, NIH, Bethesda, MD 20892
contact email	nadine.samara@nih.gov
lab head
Weiming Yang
contact affiliation	NIH/NIDCR
contact email	weiming.yang@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047845
     1. Label: PRIDE project
     2. Name: An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase