The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
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Publication Date: | 2017 |
Other Authors: | , , , , , , , , , , , , |
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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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 |
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openAccess |
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