Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

Lira-Navarrete, E. ; Rivas, M.de las (Universidad de Zaragoza) ; Compañón, I. ; Pallarés, M.C. (Universidad de Zaragoza) ; Kong, Y. ; Iglesias-Fernández, J. ; Bernardes, G.J.L. ; Peregrina, J.M. ; Rovira, C. ; Bernadó, P. ; Bruscolini, P. (Universidad de Zaragoza) ; Clausen, H. ; Lostao, A. (Universidad de Zaragoza) ; Corzana, F. ; Hurtado-Guerrero, R.

Resumen: Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.

Idioma: Inglés

DOI: 10.1038/ncomms7937

Año: 2015

Publicado en: NATURE COMMUNICATIONS 6 (2015), 6937 [10 pp]
ISSN: 2041-1723

Factor impacto JCR: 11.329 (2015)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 3 / 62 = 0.048 (2015) - Q1 - T1

Factor impacto SCIMAGO: 6.287 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B18
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/ES/MICINN/BFU2010-19504
Financiación: info:eu-repo/grantAgreement/ES/MICINN/BIO2010-14983
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2011-25871
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2012-36365
Financiación: info:eu-repo/grantAgreement/ES/MINECO/MAT2012-38318-C03-01

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología Vegetal (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Física Teórica (Dpto. Física Teórica)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)