PXD047845 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: MUC1, O-glycosylation, structure, lectin domain, substrate specificity |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047845
- Label: PRIDE project
- Name: An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase