8V9Q
Crystal structure of mGalNAc-T1 in complex with the mucin glycopeptide Muc5AC-13, Mn2+, and UDP.
Summary for 8V9Q
| Entry DOI | 10.2210/pdb8v9q/pdb |
| Descriptor | Polypeptide N-acetylgalactosaminyltransferase 1 soluble form, 2-acetamido-2-deoxy-alpha-D-galactopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total) |
| Functional Keywords | gt-a fold catalytic domain, lectin domain, golgi membrane, mucin-type o-glycosyltransferase, transferase |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 5 |
| Total formula weight | 137158.67 |
| Authors | Samara, N.L.,Collette, A.M. (deposition date: 2023-12-08, release date: 2024-03-13, Last modification date: 2024-10-23) |
| Primary citation | Collette, A.M.,Hassan, S.A.,Schmidt, S.I.,Lara, A.J.,Yang, W.,Samara, N.L. An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase. Sci Adv, 10:eadj8829-eadj8829, 2024 Cited by PubMed 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, β, and γ), where α and β 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 β 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 β repeat directs O-glycosylation to amino-terminal sites. In addition, GalNAc-T1 incorporates α and β 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. PubMed: 38416819DOI: 10.1126/sciadv.adj8829 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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