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

2017-12-05Artigo científico Acesso aberto
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dc.contributor.authorDe Las Rivas, Matilde
dc.contributor.authorLira-Navarrete, Erandi
dc.contributor.authorDaniel, Earnest James Paul
dc.contributor.authorCompanõn, Ismael
dc.contributor.authorCoelho, Helena
dc.contributor.authorDiniz, Ana
dc.contributor.authorJiménez-Barbero, Jesús
dc.contributor.authorPeregrina, Jesús M.
dc.contributor.authorClausen, Henrik
dc.contributor.authorCorzana, Francisco
dc.contributor.authorMarcelo, Filipa
dc.contributor.authorJiménez-Osés, Gonzalo
dc.contributor.authorGerken, Thomas A.
dc.contributor.authorHurtado-Guerrero, Ramon
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblNature Portfolio
dc.date.accessioned2020-09-24T22:34:20Z
dc.date.available2020-09-24T22:34:20Z
dc.date.issued2017-12-05
dc.descriptionWe 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.
dc.description.abstractThe 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1672984
dc.identifier.doi10.1038/s41467-017-02006-0
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 6653119
dc.identifier.otherPURE UUID: 5a7df232-2bbe-4a92-840a-e1ca5b46fba5
dc.identifier.otherScopus: 85037122538
dc.identifier.otherPubMed: 29208955
dc.identifier.otherORCID: /0000-0001-5049-8511/work/68143524
dc.identifier.otherPubMedCentral: PMC5716993
dc.identifier.otherWOS: 000417055600008
dc.identifier.urihttp://hdl.handle.net/10362/104678
dc.identifier.urlhttps://www.scopus.com/pages/publications/85037122538
dc.language.isoeng
dc.peerreviewedyes
dc.subjectGeneral Chemistry
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Physics and Astronomy
dc.titleThe interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferencesen
dc.typejournal article
degois.publication.issue1
degois.publication.titleNature Communications
degois.publication.volume8
dspace.entity.typePublication
rcaap.rightsopenAccess

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