Structural highlights
Function
[GALT4_HUMAN] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a highest activity toward Muc7, EA2 and Muc2, with a lowest activity than GALNT2. Glycosylates 'Thr-57' of SELPLG.
Publication Abstract from PubMed
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.
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences.,Rivas ML, Lira-Navarrete E, Daniel EJP, Companon I, Coelho H, Diniz A, Jimenez-Barbero J, Peregrina JM, Clausen H, Corzana F, Marcelo F, Jimenez-Oses G, Gerken TA, Hurtado-Guerrero R Nat Commun. 2017 Dec 5;8(1):1959. doi: 10.1038/s41467-017-02006-0. PMID:29208955[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rivas ML, Lira-Navarrete E, Daniel EJP, Companon I, Coelho H, Diniz A, Jimenez-Barbero J, Peregrina JM, Clausen H, Corzana F, Marcelo F, Jimenez-Oses G, Gerken TA, Hurtado-Guerrero R. The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences. Nat Commun. 2017 Dec 5;8(1):1959. doi: 10.1038/s41467-017-02006-0. PMID:29208955 doi:http://dx.doi.org/10.1038/s41467-017-02006-0
