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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 / 60 = 0.05 (2015) - Q1 - T1
Financiación: info:eu-repo/grantAgreement/ES/DGA/B18
Financiación: info:eu-repo/grantAgreement/ES/DGA/B89
Financiación: info:eu-repo/grantAgreement/EUR/FP7/BIOSTRUCTX-5186
Financiación: info:eu-repo/grantAgreement/EUR/FP7/ERC-2007-2013-BioStruct-X-283570
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: Article (Published version)
Área (Departamento): Física Teórica (Departamento de Física Teórica)
Área (Departamento): Bioquímica y Biología Molecular (Departamento de Bioquímica y Biología Molecular y Celular)

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Este artículo se encuentra en las siguientes colecciones:
Articles > Artículos por área > Bioquímica y Biología Molecular
Articles > Artículos por área > Física Teórica

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