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

Bibliographic Details
Main Author: De Las Rivas, Matilde
Publication Date: 2017
Other Authors: Lira-Navarrete, Erandi, Daniel, Earnest James Paul, Companõn, 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
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/104678
Summary: We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-7). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and RYC-2013-14706), the National Institutes of Health (GM113534, and instrument grant GM113534-01S), the Danish National Research Foundation (DNRF107), the FCT-Portugal (UID/Multi/04378/2013 and PTNMR Project No 022161), and the DGA (B89) for the financial support. I.C. thanks Universidad de La Rioja for the FPI grant. F.M. thanks FCT-Portugal for IF Investigator. E.L.-N. acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H.C. and J.J.-B. thank EU for the TOLLerant project. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement No. 283570 and BIOSTRUCTX_5186). We also thank BIFI (Memento cluster) and CESGA for computer support.
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spelling The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferencesChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-7). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and RYC-2013-14706), the National Institutes of Health (GM113534, and instrument grant GM113534-01S), the Danish National Research Foundation (DNRF107), the FCT-Portugal (UID/Multi/04378/2013 and PTNMR Project No 022161), and the DGA (B89) for the financial support. I.C. thanks Universidad de La Rioja for the FPI grant. F.M. thanks FCT-Portugal for IF Investigator. E.L.-N. acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H.C. and J.J.-B. thank EU for the TOLLerant project. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement No. 283570 and BIOSTRUCTX_5186). We also thank BIFI (Memento cluster) and CESGA for computer support.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- A nd/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.UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaRUNDe Las Rivas, MatildeLira-Navarrete, ErandiDaniel, Earnest James PaulCompanõn, IsmaelCoelho, HelenaDiniz, AnaJiménez-Barbero, JesúsPeregrina, Jesús M.Clausen, HenrikCorzana, FranciscoMarcelo, FilipaJiménez-Osés, GonzaloGerken, Thomas A.Hurtado-Guerrero, Ramon2020-09-24T22:34:20Z2017-12-052017-12-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/104678eng2041-1723PURE: 6653119https://doi.org/10.1038/s41467-017-02006-0info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:47:47Zoai:run.unl.pt:10362/104678Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:18:54.836837Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv 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
spellingShingle The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
De Las Rivas, Matilde
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
title_short 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_sort The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
author De Las Rivas, Matilde
author_facet De Las Rivas, Matilde
Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Companõn, 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_role author
author2 Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Companõn, 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
DQ - Departamento de Química
RUN
dc.contributor.author.fl_str_mv De Las Rivas, Matilde
Lira-Navarrete, Erandi
Daniel, Earnest James Paul
Companõn, 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
dc.subject.por.fl_str_mv Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
topic Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
description We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-7). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and RYC-2013-14706), the National Institutes of Health (GM113534, and instrument grant GM113534-01S), the Danish National Research Foundation (DNRF107), the FCT-Portugal (UID/Multi/04378/2013 and PTNMR Project No 022161), and the DGA (B89) for the financial support. I.C. thanks Universidad de La Rioja for the FPI grant. F.M. thanks FCT-Portugal for IF Investigator. E.L.-N. acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H.C. and J.J.-B. thank EU for the TOLLerant project. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement No. 283570 and BIOSTRUCTX_5186). We also thank BIFI (Memento cluster) and CESGA for computer support.
publishDate 2017
dc.date.none.fl_str_mv 2017-12-05
2017-12-05T00:00:00Z
2020-09-24T22:34:20Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/104678
url http://hdl.handle.net/10362/104678
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2041-1723
PURE: 6653119
https://doi.org/10.1038/s41467-017-02006-0
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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