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Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks

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  • Jean Lesne

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS
    Centre de Biologie Structurale, CNRS, Université de Montpellier, INSERM)

  • Marie Locard-Paulet

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS
    Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)

  • Julien Parra

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS)

  • Dušan Zivković

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS)

  • Thomas Menneteau

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS
    Institute of Structural and Molecular Biology, Division of Biosciences, University College London)

  • Marie-Pierre Bousquet

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS)

  • Odile Burlet-Schiltz

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS)

  • Julien Marcoux

    (Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS)

Abstract

Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28αβ or PA28γ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the α-ring triggered from inside the catalytic β-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the β-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair.

Suggested Citation

  • Jean Lesne & Marie Locard-Paulet & Julien Parra & Dušan Zivković & Thomas Menneteau & Marie-Pierre Bousquet & Odile Burlet-Schiltz & Julien Marcoux, 2020. "Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19934-z
    DOI: 10.1038/s41467-020-19934-z
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    Cited by:

    1. Wai Tuck Soh & Hanna P. Roetschke & John A. Cormican & Bei Fang Teo & Nyet Cheng Chiam & Monika Raabe & Ralf Pflanz & Fabian Henneberg & Stefan Becker & Ashwin Chari & Haiyan Liu & Henning Urlaub & Ju, 2024. "Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing," Nature Communications, Nature, vol. 15(1), pages 1-25, December.

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