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	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:41:30.057.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
⏵ 2	2024-10-22 06:41:37	announced	2024-10-22: Updated project metadata.

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD047845

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