5AJN

Crystal structure of the inactive form of GalNAc-T2 in complex with the glycopeptide MUC5AC-Cys13

Summary for 5AJN

• Entry DOI: 10.2210/pdb5ajn/pdb
• Related: 5AJO 5AJP
• Descriptor: POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE 2, MUCIN, SULFATE ION, ... (6 entities in total)
• Functional Keywords: transferase, afm, saxs, lectin domain, coarse-grained model, glycopeptides, inactive form, active form, compact form, extended form
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 68545.21

Authors

Lira-Navarrete, E.,delasRivas, M.,Companon, I.,Pallares, M.C.,Kong, Y.,Iglesias-Fernandez, J.,Bernardes, G.J.L.,Peregrina, J.M.,Rovira, C.,Bernado, P.,Bruscolini, P.,Clausen, H.,Lostao, A.,Corzana, F.,Hurtado-Guerrero, R. (deposition date: 2015-02-26, release date: 2015-03-11, Last modification date: 2024-11-06)

Primary citation

Lira-Navarrete, E.,De Las Rivas, M.,Companon, I.,Pallares, M.C.,Kong, Y.,Iglesias-Fernandez, J.,Bernardes, G.J.L.,Peregrina, J.M.,Rovira, C.,Bernado, P.,Bruscolini, P.,Clausen, H.,Lostao, A.,Corzana, F.,Hurtado-Guerrero, R.
Dynamic Interplay between Catalytic and Lectin Domains of Galnac-Transferases Modulates Protein O-Glycosylation.
Nat.Commun., 6:6937-, 2015

PubMed Abstract: Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.

PubMed: 25939779
DOI: 10.1038/NCOMMS7937

Experimental method

X-RAY DIFFRACTION (1.67 Å)