000057817 001__ 57817
000057817 005__ 20161214123841.0
000057817 0247_ $$2doi$$a10.1038/ncomms7937
000057817 0248_ $$2sideral$$a90416
000057817 037__ $$aART-2015-90416
000057817 041__ $$aeng
000057817 100__ $$aLira Navarrete, Erandi
000057817 245__ $$aDynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation
000057817 260__ $$c2015
000057817 5060_ $$aAccess copy available to the general public$$fUnrestricted
000057817 5203_ $$aProtein 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.
000057817 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B18$$9info:eu-repo/grantAgreement/ES/DGA/B89$$9info:eu-repo/grantAgreement/EUR/FP7/BIOSTRUCTX-5186$$9info:eu-repo/grantAgreement/EUR/FP7/ERC-2007-2013-BioStruct-X-283570$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504$$9info:eu-repo/grantAgreement/ES/MICINN/BIO2010-14983$$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2011-25871$$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P$$9info:eu-repo/grantAgreement/ES/MINECO/CTQ2012-36365$$9info:eu-repo/grantAgreement/ES/MINECO/MAT2012-38318-C03-01
000057817 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000057817 590__ $$a11.329$$b2015
000057817 591__ $$aMULTIDISCIPLINARY SCIENCES$$b3 / 60 = 0.05$$c2015$$dQ1$$eT1
000057817 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000057817 700__ $$0(orcid)0000-0002-1924-334X$$aRivas González De Garay, Matilde Teresa De Las$$uUniversidad de Zaragoza
000057817 700__ $$aCompañón, I.
000057817 700__ $$aPallares Matute, Maria Carmen
000057817 700__ $$aKong, Y.
000057817 700__ $$aIglesias-Fernández, J.
000057817 700__ $$aBernardes, G. J. L.
000057817 700__ $$aPeregrina, J. M.
000057817 700__ $$aRovira, C.
000057817 700__ $$aBernadó, P.
000057817 700__ $$0(orcid)0000-0002-5833-8798$$aBruscolini , Pierpaolo$$uUniversidad de Zaragoza
000057817 700__ $$aClausen, H.
000057817 700__ $$aLostao, A.
000057817 700__ $$aCorzana, F.
000057817 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado Guerrero, Ramon
000057817 7102_ $$12004$$2405$$aUniversidad de Zaragoza$$bDepartamento de Física Teórica$$cFísica Teórica
000057817 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular
000057817 773__ $$g6 (2015), 6937 [10 pp]$$pNATURE COMMUNICATIONS$$tNATURE COMMUNICATIONS$$x2041-1723
000057817 8564_ $$s766990$$uhttp://zaguan.unizar.es/record/57817/files/texto_completo.pdf$$yVersión publicada
000057817 8564_ $$s81234$$uhttp://zaguan.unizar.es/record/57817/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000057817 909CO $$ooai:zaguan.unizar.es:57817$$particulos$$pdriver
000057817 951__ $$a2016-12-13-14:00:39
000057817 980__ $$aARTICLE