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Modelling protein complexes with crosslinking mass spectrometry and deep learning

Author

Listed:
  • Kolja Stahl

    (Chair of Bioanalytics)

  • Robert Warneke

    (GZMB)

  • Lorenz Demann

    (GZMB)

  • Rica Bremenkamp

    (GZMB)

  • Björn Hormes

    (GZMB)

  • Oliver Brock

    (Robotics and Biology Laboratory
    Research Cluster of Excellence)

  • Jörg Stülke

    (GZMB)

  • Juri Rappsilber

    (Chair of Bioanalytics
    a Science Framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin
    University of Edinburgh)

Abstract

Scarcity of structural and evolutionary information on protein complexes poses a challenge to deep learning-based structure modelling. We integrate experimental distance restraints obtained by crosslinking mass spectrometry (MS) into AlphaFold-Multimer, by extending AlphaLink to protein complexes. Integrating crosslinking MS data substantially improves modelling performance on challenging targets, by helping to identify interfaces, focusing sampling, and improving model selection. This extends to single crosslinks from whole-cell crosslinking MS, opening the possibility of whole-cell structural investigations driven by experimental data. We demonstrate this by revealing the molecular basis of iron homoeostasis in Bacillus subtilis.

Suggested Citation

  • Kolja Stahl & Robert Warneke & Lorenz Demann & Rica Bremenkamp & Björn Hormes & Oliver Brock & Jörg Stülke & Juri Rappsilber, 2024. "Modelling protein complexes with crosslinking mass spectrometry and deep learning," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51771-2
    DOI: 10.1038/s41467-024-51771-2
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    References listed on IDEAS

    as
    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Swantje Lenz & Ludwig R. Sinn & Francis J. O’Reilly & Lutz Fischer & Fritz Wegner & Juri Rappsilber, 2021. "Reliable identification of protein-protein interactions by crosslinking mass spectrometry," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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