Open AccessThe interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
Author(s) -
Matilde de las Rivas,
Erandi LiraNavarrete,
Earnest James Paul Daniel,
Ismael Compañón,
Helena Coelho,
Ana Diniz,
Jesús JiménezBarbero,
Jesús M. Peregrina,
Henrik Clausen,
Francisco Corzana,
Filipa Marcelo,
Gonzalo JiménezOsés,
Thomas A. Gerken,
Ramón HurtadoGuerrero
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-017-02006-0
Subject(s) - linker , glycosylation , lectin , sequence (biology) , c type lectin , chemistry , biochemistry , biology , computer science , operating system
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.