Deciphering the Non-Equivalence of Serine and Threonine O-glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody
- Martínez-Sáez, N. 24
- Castro-Lõpez, J. 57
- Valero-González, J. 57
- Madariaga, D. 2
- Compañõn, I. 2
- Somovilla, V.J. 24
- Salvadó, Mirian. 14
- Asensio, J.L. 9
- Jiménez-Barbero, J. 3610
- Avenoza, A. 2
- Busto, J.H. 2
- Bernardes, G.J.L. 48
- Peregrina, J.M. 2
- Hurtado-Guerrero, R. 57
- Corzana, F. 2
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1
Universitat Rovira i Virgili
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2
Universidad de La Rioja
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3
Centro de Investigaciones Biológicas
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4
University of Cambridge
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- 5 Fundaciõn ARAID, Edificio Pignatelli 36, Zaragoza, Spain
- 6 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
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7
Universidad de Zaragoza
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8
Universidade de Lisboa
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9
Instituto de Química Orgánica General
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Centro de Investigación Cooperativa en Biotecnología
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Centro de Investigación Cooperativa en Biotecnología
Zamudio, España
ISSN: 1433-7851
Año de publicación: 2015
Volumen: 54
Número: 34
Páginas: 9830
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Angewandte Chemie International
Resumen
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. © 2015 The Authors.