57817 20230313141235.0 doi 10.1038/ncomms7937 sideral 90416 ART-2015-90416 eng Lira-Navarrete, E. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation 2015 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/B18 info:eu-repo/grantAgreement/ES/DGA/B89 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 info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504 info:eu-repo/grantAgreement/ES/MICINN/BIO2010-14983 info:eu-repo/grantAgreement/ES/MICINN/CTQ2011-25871 info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P info:eu-repo/grantAgreement/ES/MINECO/CTQ2012-36365 info:eu-repo/grantAgreement/ES/MINECO/MAT2012-38318-C03-01 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 11.329 2015 MULTIDISCIPLINARY SCIENCES 3 / 62 = 0.048 2015 Q1 T1 6.287 2015 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2015 Q1 Physics and Astronomy (miscellaneous) 2015 Q1 Chemistry (miscellaneous) 2015 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rivas, M.de las Universidad de Zaragoza (orcid)0000-0002-1924-334X 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 (orcid)0000-0002-5833-8798 Clausen, H. Lostao, A. Universidad de Zaragoza (orcid)0000-0001-7460-5916 Corzana, F. Hurtado-Guerrero, R. (orcid)0000-0002-3122-9401 1002 412 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Fisiología Vegetal 2004 405 Universidad de Zaragoza Dpto. Física Teórica Área Física Teórica 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 6 (2015), 6937 [10 pp] NATURE COMMUNICATIONS NATURE COMMUNICATIONS 2041-1723 766990 http://zaguan.unizar.es/record/57817/files/texto_completo.pdf Versión publicada 81234 http://zaguan.unizar.es/record/57817/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:57817 articulos driver 2023-03-13-13:54:17 ARTICLE