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

Rivas, M.D.L. (Universidad de Zaragoza) ; Lira-Navarrete, E. ; Daniel, E.J.P. ; Companõn, I. ; Coelho, H. ; Diniz, A. ; Jiménez-Barbero, J. ; Peregrina, J.M. ; Clausen, H. ; Corzana, F. ; Marcelo, F. ; Jiménez-Osés, G. ; Gerken, T.A. ; Hurtado-Guerrero, R. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-017-02006-0

Año: 2017

Publicado en: Nature Communications 8, 1 (2017), 1959 [11 pp]
ISSN: 2041-1723

Factor impacto JCR: 12.353 (2017)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 3 / 64 = 0.047 (2017) - Q1 - T1

Factor impacto SCIMAGO: 6.582 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B89
Financiación: info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X
Financiación: info:eu-repo/grantAgreement/EC/FP7/609409/EU/Supporting transnational mobility within the European life sciences by cofunding of the EMBO Fellowship Programme/LTFCOFUND2013
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2015-67727-R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2013-14706
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2016-75633-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-70524-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)