The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
- Rivas, M.D.L. 1
- Lira-Navarrete, E. 13
- Daniel, E.J.P. 6
- Companõn, I. 4
- Coelho, H. 259
- Diniz, A. 9
- Jiménez-Barbero, J. 257
- Peregrina, J.M. 4
- Clausen, H. 3
- Corzana, F. 4
- Marcelo, F. 9
- Jiménez-Osés, G. 4
- Gerken, T.A. 666
- Hurtado-Guerrero, R. 18
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1
Universidad de Zaragoza
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- 2 CIC BioGUNE, Bizkaia Technology Park, Building 801A, Derio, Spain
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3
University of Copenhagen
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4
Universidad de La Rioja
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5
Universidad del País Vasco/Euskal Herriko Unibertsitatea
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Universidad del País Vasco/Euskal Herriko Unibertsitatea
Lejona, España
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6
Case Western Reserve University
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7
Ikerbasque, Fundación Vasca para la Ciencia
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- 8 Fundación ARAID, Zaragoza, Spain
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9
Universidade Nova de Lisboa
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ISSN: 2041-1723
Año de publicación: 2017
Volumen: 8
Número: 1
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Nature Communications
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Resumen
The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts. © 2017 The Author(s).