doi:10.1038/ncomms7937engLira-Navarrete, E.Rivas, M.de lasCompañón, I.Pallarés, M.C.Kong, Y.Iglesias-Fernández, J.Bernardes, G.J.L.Peregrina, J.M.Rovira, C.Bernadó, P.Bruscolini, P.Clausen, H.Lostao, A.Corzana, F.Hurtado-Guerrero, R.Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylationART-2015-90416Protein 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.2015http://zaguan.unizar.es/record/5781710.1038/ncomms7937http://zaguan.unizar.es/record/57817oai:zaguan.unizar.es:57817info:eu-repo/grantAgreement/ES/DGA/B18info:eu-repo/grantAgreement/ES/DGA/B89info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-Xinfo:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504info:eu-repo/grantAgreement/ES/MICINN/BIO2010-14983info:eu-repo/grantAgreement/ES/MICINN/CTQ2011-25871info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-Pinfo:eu-repo/grantAgreement/ES/MINECO/CTQ2012-36365info:eu-repo/grantAgreement/ES/MINECO/MAT2012-38318-C03-01NATURE COMMUNICATIONS 6 (2015), 6937 [10 pp]byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess