The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

  1. Rivas, M.D.L. 1
  2. Lira-Navarrete, E. 13
  3. Daniel, E.J.P. 6
  4. Companõn, I. 4
  5. Coelho, H. 259
  6. Diniz, A. 9
  7. Jiménez-Barbero, J. 257
  8. Peregrina, J.M. 4
  9. Clausen, H. 3
  10. Corzana, F. 4
  11. Marcelo, F. 9
  12. Jiménez-Osés, G. 4
  13. Gerken, T.A. 666
  14. Hurtado-Guerrero, R. 18
  1. 1 Universidad de Zaragoza
    info

    Universidad de Zaragoza

    Zaragoza, España

    ROR https://ror.org/012a91z28

  2. 2 CIC BioGUNE, Bizkaia Technology Park, Building 801A, Derio, Spain
  3. 3 University of Copenhagen
    info

    University of Copenhagen

    Copenhague, Dinamarca

    ROR https://ror.org/035b05819

  4. 4 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  5. 5 Universidad del País Vasco/Euskal Herriko Unibertsitatea
    info

    Universidad del País Vasco/Euskal Herriko Unibertsitatea

    Lejona, España

    ROR https://ror.org/000xsnr85

  6. 6 Case Western Reserve University
    info

    Case Western Reserve University

    Cleveland, Estados Unidos

    ROR https://ror.org/051fd9666

  7. 7 Ikerbasque, Fundación Vasca para la Ciencia
    info

    Ikerbasque, Fundación Vasca para la Ciencia

    Bilbao, España

    ROR https://ror.org/01cc3fy72

  8. 8 Fundación ARAID, Zaragoza, Spain
  9. 9 Universidade Nova de Lisboa
    info

    Universidade Nova de Lisboa

    Lisboa, Portugal

    ROR https://ror.org/02xankh89

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Journal:
Nature Communications

ISSN: 2041-1723

Year of publication: 2017

Volume: 8

Issue: 1

Type: Article

DOI: 10.1038/S41467-017-02006-0 SCOPUS: 2-s2.0-85037122538 WoS: WOS:000417055600008 GOOGLE SCHOLAR

More publications in: Nature Communications

Abstract

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).