000118017 001__ 118017 000118017 005__ 20240319080953.0 000118017 0247_ $$2doi$$a10.1038/s41467-022-29833-0 000118017 0248_ $$2sideral$$a128701 000118017 037__ $$aART-2022-128701 000118017 041__ $$aeng 000118017 100__ $$0(orcid)0000-0002-5838-0857$$aGonzález-Ramírez, A.M.$$uUniversidad de Zaragoza 000118017 245__ $$aStructural basis for the synthesis of the core 1 structure by C1GalT1 000118017 260__ $$c2022 000118017 5060_ $$aAccess copy available to the general public$$fUnrestricted 000118017 5203_ $$aC1GalT1 is an essential inverting glycosyltransferase responsible for synthesizing the core 1 structure, a common precursor for mucin-type O-glycans found in many glycoproteins. To date, the structure of C1GalT1 and the details of substrate recognition and catalysis remain unknown. Through biophysical and cellular studies, including X-ray crystallography of C1GalT1 complexed to a glycopeptide, we report that C1GalT1 is an obligate GT-A fold dimer that follows a SN2 mechanism. The binding of the glycopeptides to the enzyme is mainly driven by the GalNAc moiety while the peptide sequence provides optimal kinetic and binding parameters. Interestingly, to achieve glycosylation, C1GalT1 recognizes a high-energy conformation of the a-GalNAc-Thr linkage, negligibly populated in solution. By imposing this 3D-arrangement on that fragment, characteristic of a-GalNAc-Ser peptides, C1GalT1 ensures broad glycosylation of both acceptor substrates. These findings illustrate a structural and mechanistic blueprint to explain glycosylation of multiple acceptor substrates, extending the repertoire of mechanisms adopted by glycosyltransferases. © 2022, The Author(s). 000118017 536__ $$9info:eu-repo/grantAgreement/ES/AEI/BFU2016-75633-P$$9info:eu-repo/grantAgreement/ES/AEI/PID2019-105451GB-I00$$9info:eu-repo/grantAgreement/ES/AEI/RTI-2018-099592-B-C21$$9info:eu-repo/grantAgreement/ES/DGA/E34-R17$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X 000118017 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000118017 590__ $$a16.6$$b2022 000118017 592__ $$a5.116$$b2022 000118017 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 73 = 0.082$$c2022$$dQ1$$eT1 000118017 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1 000118017 593__ $$aPhysics and Astronomy (miscellaneous)$$c2022$$dQ1 000118017 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1 000118017 594__ $$a24.9$$b2022 000118017 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000118017 700__ $$aGrosso, A.S. 000118017 700__ $$aYang, Z. 000118017 700__ $$aCompañón, I. 000118017 700__ $$aCoelho, H. 000118017 700__ $$aNarimatsu, Y. 000118017 700__ $$aClausen, H. 000118017 700__ $$aMarcelo, F. 000118017 700__ $$aCorzana, F. 000118017 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R. 000118017 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000118017 773__ $$g13 (2022), 2398 [15 pp.]$$tNature communications$$x2041-1723 000118017 8564_ $$s3039848$$uhttps://zaguan.unizar.es/record/118017/files/texto_completo.pdf$$yVersión publicada 000118017 8564_ $$s1641660$$uhttps://zaguan.unizar.es/record/118017/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000118017 909CO $$ooai:zaguan.unizar.es:118017$$particulos$$pdriver 000118017 951__ $$a2024-03-18-13:14:39 000118017 980__ $$aARTICLE