5NQA

Crystal structure of GalNAc-T4 in complex with the monoglycopeptide 3

Summary for 5NQA

• Entry DOI: 10.2210/pdb5nqa/pdb
• Descriptor: Polypeptide N-acetylgalactosaminyltransferase 4, Monoglycopeptide 3, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: galnac-t4, galnac-t2, chimeras, glycosylation preferences, std-nmr, flexible linker, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Golgi apparatus membrane ; Single-pass type II membrane protein : Q8N4A0
• Total number of polymer chains: 3
• Total formula weight: 140480.98

Authors

de las Rivas, M.,Lira-Navarrete, E.,Daniel, E.J.P.,Companon, I.,Coelho, H.,Diniz, A.,Jimenez-Barbero, J.,Peregrina, J.M.,Clausen, H.,Corzana, F.,Marcelo, F.,Jimenez-Oses, G.,Gerken, T.A.,Hurtado-Guerrero, R. (deposition date: 2017-04-19, release date: 2017-12-20, Last modification date: 2024-10-16)

Primary citation

Rivas, M.L.,Lira-Navarrete, E.,Daniel, E.J.P.,Companon, I.,Coelho, H.,Diniz, A.,Jimenez-Barbero, J.,Peregrina, J.M.,Clausen, H.,Corzana, F.,Marcelo, F.,Jimenez-Oses, G.,Gerken, T.A.,Hurtado-Guerrero, R.
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences.
Nat Commun, 8:1959-1959, 2017

PubMed Abstract: The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts.

PubMed: 29208955
DOI: 10.1038/s41467-017-02006-0

Experimental method

X-RAY DIFFRACTION (1.9 Å)