Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4

Detalhes bibliográficos
Autor(a) principal: De Las Rivas, Matilde
Data de Publicação: 2018
Outros Autores: Paul Daniel, Earnest James, Coelho, Helena, Lira-Navarrete, Erandi, Raich, Lluis, Compañón, Ismael, Diniz, Ana, Lagartera, Laura, Jiménez-Barbero, Jesús, Clausen, Henrik, Rovira, Carme, Marcelo, Filipa, Corzana, Francisco, Gerken, Thomas A., Hurtado-Guerrero, Ramon
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/104681
Resumo: info:eu-repo/grantAgreement/FCT/5876/147258/PT We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-15). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and CTQ2017-85496-P), AGAUR (SGR2017-1189), the National Institutes of Health (R01-GM113534, and instrument Grant GM113534-01S to T. A. Gerken), the Danish National Research Foundation (DNRF107), the FCT-Portugal [UID/Multi/04378/2013 cofinanced by the FEDER (POCI-01-0145-FEDER-007728)], and the DGA (E34_R17) for financial support. I. Comparion thanks Universidad de La Rioja for the FPI grant. F. Marcelo thanks FCT-Portugal for IF Investigator grant (IF/00780/2015) and PTNMR supported by Project 022161. E. Lira-Navarrete acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 cofunded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H. Coelho and J. Jimenez-Barbero 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 283570 and BIOSTRUCTX 5186). We would also like to acknowledge the assistance of Juwan Lee in obtaining the GaINAc-T4 random peptide motifs.
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spelling Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4Chemistry(all)Chemical Engineering(all)info:eu-repo/grantAgreement/FCT/5876/147258/PT We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-15). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and CTQ2017-85496-P), AGAUR (SGR2017-1189), the National Institutes of Health (R01-GM113534, and instrument Grant GM113534-01S to T. A. Gerken), the Danish National Research Foundation (DNRF107), the FCT-Portugal [UID/Multi/04378/2013 cofinanced by the FEDER (POCI-01-0145-FEDER-007728)], and the DGA (E34_R17) for financial support. I. Comparion thanks Universidad de La Rioja for the FPI grant. F. Marcelo thanks FCT-Portugal for IF Investigator grant (IF/00780/2015) and PTNMR supported by Project 022161. E. Lira-Navarrete acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 cofunded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H. Coelho and J. Jimenez-Barbero 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 283570 and BIOSTRUCTX 5186). We would also like to acknowledge the assistance of Juwan Lee in obtaining the GaINAc-T4 random peptide motifs.Mucin-type O-glycosylation is initiated by a family of polypeptide GalNAc-transferases (GalNAc-Ts) which are type-II transmembrane proteins that contain Golgi luminal catalytic and lectin domains that are connected by a flexible linker. Several GalNAc-Ts, including GalNAc-T4, show both long-range and short-range prior glycosylation specificity, governed by their lectin and catalytic domains, respectively. While the mechanism of the lectin-domain-dependent glycosylation is well-known, the molecular basis for the catalytic-domain-dependent glycosylation of glycopeptides is unclear. Herein, we report the crystal structure of GalNAc-T4 bound to the diglycopeptide GAT GAGAGAGT TPGPG (containing two α-GalNAc glycosylated Thr (T ), the PXP motif and a "naked" Thr acceptor site) that describes its catalytic domain glycopeptide GalNAc binding site. Kinetic studies of wild-type and GalNAc binding site mutant enzymes show the lectin domain GalNAc binding activity dominates over the catalytic domain GalNAc binding activity and that these activities can be independently eliminated. Surprisingly, a flexible loop protruding from the lectin domain was found essential for the optimal activity of the catalytic domain. This work provides the first structural basis for the short-range glycosylation preferences of a GalNAc-T.UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaRUNDe Las Rivas, MatildePaul Daniel, Earnest JamesCoelho, HelenaLira-Navarrete, ErandiRaich, LluisCompañón, IsmaelDiniz, AnaLagartera, LauraJiménez-Barbero, JesúsClausen, HenrikRovira, CarmeMarcelo, FilipaCorzana, FranciscoGerken, Thomas A.Hurtado-Guerrero, Ramon2020-09-24T22:35:49Z2018-09-262018-09-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17application/pdfhttp://hdl.handle.net/10362/104681eng2374-7943PURE: 12263431https://doi.org/10.1021/acscentsci.8b00488info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:50:12Zoai:run.unl.pt:10362/104681Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:40:18.868773Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
title Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
spellingShingle Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
De Las Rivas, Matilde
Chemistry(all)
Chemical Engineering(all)
title_short Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
title_full Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
title_fullStr Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
title_full_unstemmed Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
title_sort Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short-Range Glycosylation Preferences of GalNAc-T4
author De Las Rivas, Matilde
author_facet De Las Rivas, Matilde
Paul Daniel, Earnest James
Coelho, Helena
Lira-Navarrete, Erandi
Raich, Lluis
Compañón, Ismael
Diniz, Ana
Lagartera, Laura
Jiménez-Barbero, Jesús
Clausen, Henrik
Rovira, Carme
Marcelo, Filipa
Corzana, Francisco
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
author_role author
author2 Paul Daniel, Earnest James
Coelho, Helena
Lira-Navarrete, Erandi
Raich, Lluis
Compañón, Ismael
Diniz, Ana
Lagartera, Laura
Jiménez-Barbero, Jesús
Clausen, Henrik
Rovira, Carme
Marcelo, Filipa
Corzana, Francisco
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
author2_role author
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
Paul Daniel, Earnest James
Coelho, Helena
Lira-Navarrete, Erandi
Raich, Lluis
Compañón, Ismael
Diniz, Ana
Lagartera, Laura
Jiménez-Barbero, Jesús
Clausen, Henrik
Rovira, Carme
Marcelo, Filipa
Corzana, Francisco
Gerken, Thomas A.
Hurtado-Guerrero, Ramon
dc.subject.por.fl_str_mv Chemistry(all)
Chemical Engineering(all)
topic Chemistry(all)
Chemical Engineering(all)
description info:eu-repo/grantAgreement/FCT/5876/147258/PT We thank synchrotron radiation sources DLS (Oxford) and in particular beamline I03 (experiment number MX10121-15). We thank ARAID, MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P, CTQ2015-67727-R, CTQ2015-70524-R, and CTQ2017-85496-P), AGAUR (SGR2017-1189), the National Institutes of Health (R01-GM113534, and instrument Grant GM113534-01S to T. A. Gerken), the Danish National Research Foundation (DNRF107), the FCT-Portugal [UID/Multi/04378/2013 cofinanced by the FEDER (POCI-01-0145-FEDER-007728)], and the DGA (E34_R17) for financial support. I. Comparion thanks Universidad de La Rioja for the FPI grant. F. Marcelo thanks FCT-Portugal for IF Investigator grant (IF/00780/2015) and PTNMR supported by Project 022161. E. Lira-Navarrete acknowledges her postdoctoral EMBO fellowship ALTF 1553-2015 cofunded by the European Commission (LTFCOFUND2013, GA-2013-609409) and Marie Curie Actions. H. Coelho and J. Jimenez-Barbero 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 283570 and BIOSTRUCTX 5186). We would also like to acknowledge the assistance of Juwan Lee in obtaining the GaINAc-T4 random peptide motifs.
publishDate 2018
dc.date.none.fl_str_mv 2018-09-26
2018-09-26T00:00:00Z
2020-09-24T22:35:49Z
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/10362/104681
url http://hdl.handle.net/10362/104681
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2374-7943
PURE: 12263431
https://doi.org/10.1021/acscentsci.8b00488
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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