Deciphering the Non-Equivalence of Serine and Threonine O-glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody
| Autor: | Martínez-Sáez, N., Castro-López, Jorge, Valero-González, Jessika, Madariaga, David, Compañón, Ismael, Somovilla, V.J., Salvadó, M., Asensio, Juan Luis, Jiménez-Barbero, Jesús, Avenoza, A., Busto, J.H., Bernardes, G.J.L., Peregrina, J.M., Hurtado-Guerrero, R., Corzana, Francisco |
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| Přispěvatelé: | Lopes Bernardes, Goncalo [0000-0001-6594-8917], Apollo - University of Cambridge Repository |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | RIUR. Repositorio Institucional de la Universidad de La Rioja instname Digital.CSIC. Repositorio Institucional del CSIC |
| Popis: | © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. The structural features of MUC1-like glycopeptides bearing the Tn antigen (α-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the α-O-GalNAc-Ser derivative, the glycosidic linkage adopts a high-energy conformation, barely populated in the free state. This unusual structure (also observed in an α-S-GalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies. |
| Databáze: | OpenAIRE |
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