Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation
- Lira-Navarrete, E. 1
- De Las Rivas, M. 1
- Compañón, I. 5
- Pallarés, M.C. 1
- Kong, Y. 3
- Iglesias-Fernández, J. 46
- Bernardes, G.J.L. 710
- Peregrina, J.M. 5
- Rovira, C. 49
- Bernadó, P. 2
- Bruscolini, P. 1
- Clausen, H. 3
- Lostao, Anabel. 18
- Corzana, F. 5
- Hurtado-Guerrero, R. 18
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1
Universidad de Zaragoza
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2
University of Montpellier
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3
Copenhagen University Hospital
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4
Universitat de Barcelona
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5
Universidad de La Rioja
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6
King's College London
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7
University of Cambridge
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- 8 Fundación ARAID, Zaragoza, Spain
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9
Institució Catalana de Recerca i Estudis Avançats
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10
Universidade de Lisboa
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ISSN: 2041-1723
Año de publicación: 2015
Volumen: 6
Páginas: 1-12
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Nature Communications
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Resumen
Protein 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. © 2015 Macmillan Publishers Limited. All rights reserved.