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The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

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 (Gal...

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Autores principales: de las Rivas, Matilde, Lira-Navarrete, Erandi, Daniel, Earnest James Paul, Compañón, Ismael, Coelho, Helena, Diniz, Ana, Jiménez-Barbero, Jesús, Peregrina, Jesús M., Clausen, Henrik, Corzana, Francisco, Marcelo, Filipa, Jiménez-Osés, Gonzalo, Gerken, Thomas A., Hurtado-Guerrero, Ramon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716993/
https://www.ncbi.nlm.nih.gov/pubmed/29208955
http://dx.doi.org/10.1038/s41467-017-02006-0
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author de las Rivas, Matilde
Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Compañón, Ismael
Coelho, Helena
Diniz, Ana
Jiménez-Barbero, Jesús
Peregrina, Jesús M.
Clausen, Henrik
Corzana, Francisco
Marcelo, Filipa
Jiménez-Osés, Gonzalo
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
author_facet de las Rivas, Matilde
Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Compañón, Ismael
Coelho, Helena
Diniz, Ana
Jiménez-Barbero, Jesús
Peregrina, Jesús M.
Clausen, Henrik
Corzana, Francisco
Marcelo, Filipa
Jiménez-Osés, Gonzalo
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
author_sort de las Rivas, Matilde
collection PubMed
description 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.
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spelling pubmed-57169932017-12-08 The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences de las Rivas, Matilde Lira-Navarrete, Erandi Daniel, Earnest James Paul Compañón, Ismael Coelho, Helena Diniz, Ana Jiménez-Barbero, Jesús Peregrina, Jesús M. Clausen, Henrik Corzana, Francisco Marcelo, Filipa Jiménez-Osés, Gonzalo Gerken, Thomas A. Hurtado-Guerrero, Ramon Nat Commun Article 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. Nature Publishing Group UK 2017-12-05 /pmc/articles/PMC5716993/ /pubmed/29208955 http://dx.doi.org/10.1038/s41467-017-02006-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
de las Rivas, Matilde
Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Compañón, Ismael
Coelho, Helena
Diniz, Ana
Jiménez-Barbero, Jesús
Peregrina, Jesús M.
Clausen, Henrik
Corzana, Francisco
Marcelo, Filipa
Jiménez-Osés, Gonzalo
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title_full The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title_fullStr The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title_full_unstemmed The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title_short The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
title_sort interdomain flexible linker of the polypeptide galnac transferases dictates their long-range glycosylation preferences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716993/
https://www.ncbi.nlm.nih.gov/pubmed/29208955
http://dx.doi.org/10.1038/s41467-017-02006-0
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