Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

  1. Lira-Navarrete, E. 1
  2. De Las Rivas, M. 1
  3. Compañón, I. 5
  4. Pallarés, M.C. 1
  5. Kong, Y. 3
  6. Iglesias-Fernández, J. 46
  7. Bernardes, G.J.L. 710
  8. Peregrina, J.M. 5
  9. Rovira, C. 49
  10. Bernadó, P. 2
  11. Bruscolini, P. 1
  12. Clausen, H. 3
  13. Lostao, Anabel. 18
  14. Corzana, F. 5
  15. Hurtado-Guerrero, R. 18
  1. 1 Universidad de Zaragoza
    info

    Universidad de Zaragoza

    Zaragoza, España

    ROR https://ror.org/012a91z28

  2. 2 University of Montpellier
    info

    University of Montpellier

    Montpellier, Francia

    ROR https://ror.org/051escj72

  3. 3 Copenhagen University Hospital
    info

    Copenhagen University Hospital

    Copenhague, Dinamarca

    ROR https://ror.org/05bpbnx46

  4. 4 Universitat de Barcelona
    info

    Universitat de Barcelona

    Barcelona, España

    ROR https://ror.org/021018s57

  5. 5 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  6. 6 King's College London
    info

    King's College London

    Londres, Reino Unido

    ROR https://ror.org/0220mzb33

  7. 7 University of Cambridge
    info

    University of Cambridge

    Cambridge, Reino Unido

    ROR https://ror.org/013meh722

  8. 8 Fundación ARAID, Zaragoza, Spain
  9. 9 Institució Catalana de Recerca i Estudis Avançats
    info

    Institució Catalana de Recerca i Estudis Avançats

    Barcelona, España

    ROR https://ror.org/0371hy230

  10. 10 Universidade de Lisboa
    info

    Universidade de Lisboa

    Lisboa, Portugal

    ROR https://ror.org/01c27hj86

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Revista:
Nature Communications

ISSN: 2041-1723

Año de publicación: 2015

Volumen: 6

Páginas: 1-12

Tipo: Artículo

DOI: 10.1038/NCOMMS7937 SCOPUS: 2-s2.0-84929208855 WoS: WOS:000355527200001 GOOGLE SCHOLAR

Otras publicaciones en: Nature Communications

Repositorio institucional: lock_openAcceso abierto Editor

Proyectos relacionados

Diseño racional de glicopéptidos con aplicaciones en Química Biológica

2013/00007/001

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.