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Massively parallel interrogation of protein fragment secretability using SECRiFY reveals features influencing secretory system transit

Author

Listed:
  • Morgane Boone

    (Center for Medical Biotechnology, VIB
    Ghent University
    Department of Biochemistry and Biophysics, UCSF)

  • Pathmanaban Ramasamy

    (Center for Medical Biotechnology, VIB
    Ghent University
    Structural Biology Brussels, VUB
    Structural Biology Research Center, VIB)

  • Jasper Zuallaert

    (Center for Medical Biotechnology, VIB
    Ghent University
    Ghent University Global Campus
    IDLab, ELIS, UGent)

  • Robbin Bouwmeester

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Berre Moer

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Davy Maddelein

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Demet Turan

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Niels Hulstaert

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Hannah Eeckhaut

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Elien Vandermarliere

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Lennart Martens

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Sven Degroeve

    (Center for Medical Biotechnology, VIB
    Ghent University)

  • Wesley Neve

    (Ghent University Global Campus
    IDLab, ELIS, UGent)

  • Wim Vranken

    (Structural Biology Brussels, VUB
    Structural Biology Research Center, VIB
    Interuniversity Institute of Bioinformatics in Brussels (IB)2, ULB-VUB)

  • Nico Callewaert

    (Center for Medical Biotechnology, VIB
    Ghent University)

Abstract

While transcriptome- and proteome-wide technologies to assess processes in protein biogenesis are now widely available, we still lack global approaches to assay post-ribosomal biogenesis events, in particular those occurring in the eukaryotic secretory system. We here develop a method, SECRiFY, to simultaneously assess the secretability of >105 protein fragments by two yeast species, S. cerevisiae and P. pastoris, using custom fragment libraries, surface display and a sequencing-based readout. Screening human proteome fragments with a median size of 50–100 amino acids, we generate datasets that enable datamining into protein features underlying secretability, revealing a striking role for intrinsic disorder and chain flexibility. The SECRiFY methodology generates sufficient amounts of annotated data for advanced machine learning methods to deduce secretability patterns. The finding that secretability is indeed a learnable feature of protein sequences provides a solid base for application-focused studies.

Suggested Citation

  • Morgane Boone & Pathmanaban Ramasamy & Jasper Zuallaert & Robbin Bouwmeester & Berre Moer & Davy Maddelein & Demet Turan & Niels Hulstaert & Hannah Eeckhaut & Elien Vandermarliere & Lennart Martens & , 2021. "Massively parallel interrogation of protein fragment secretability using SECRiFY reveals features influencing secretory system transit," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26720-y
    DOI: 10.1038/s41467-021-26720-y
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