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

11 pags, 3 figs, 2 tabs

Detalles Bibliográficos
Autores: Rivas, Matilde de las, Lira-Navarrete, Erandi, Paul Daniel, Earnest James, 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, Ramón
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/255741
Acceso en línea:http://hdl.handle.net/10261/255741
Access Level:acceso abierto
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spelling The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferencesRivas, Matilde de lasLira-Navarrete, ErandiPaul Daniel, Earnest JamesCompañón, IsmaelCoelho, HelenaDiniz, AnaJiménez-Barbero, JesúsPeregrina, Jesús M.Clausen, HenrikCorzana, FranciscoMarcelo, FilipaJiménez-Osés, GonzaloGerken, Thomas A.Hurtado-Guerrero, Ramón11 pags, 3 figs, 2 tabsThe 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.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.Peer reviewedSpringer NatureConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/255741reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://doi.org/10.1038/s41467-017-02006-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2557412026-05-22T06:33:51Z
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
Rivas, Matilde de las
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
dc.creator.none.fl_str_mv Rivas, Matilde de las
Lira-Navarrete, Erandi
Paul Daniel, Earnest James
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, Ramón
author Rivas, Matilde de las
author_facet Rivas, Matilde de las
Lira-Navarrete, Erandi
Paul Daniel, Earnest James
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, Ramón
author_role author
author2 Lira-Navarrete, Erandi
Paul Daniel, Earnest James
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, Ramón
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description 11 pags, 3 figs, 2 tabs
publishDate 2012
dc.date.none.fl_str_mv 2012
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/255741
url http://hdl.handle.net/10261/255741
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://doi.org/10.1038/s41467-017-02006-0
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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