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Integrative solution structure of PTBP1-IRES complex reveals strong compaction and ordering with residual conformational flexibility

Author

Listed:
  • Georg Dorn

    (ETH Zürich)

  • Christoph Gmeiner

    (ETH Zürich)

  • Tebbe Vries

    (ETH Zürich)

  • Emil Dedic

    (ETH Zürich)

  • Mihajlo Novakovic

    (ETH Zürich)

  • Fred F. Damberger

    (ETH Zürich)

  • Christophe Maris

    (ETH Zürich)

  • Esteban Finol

    (ETH Zürich)

  • Chris P. Sarnowski

    (ETH Zürich)

  • Joachim Kohlbrecher

    (Paul Scherrer Institut)

  • Timothy J. Welsh

    (ETH Zürich)

  • Sreenath Bolisetty

    (ETH Zürich)

  • Raffaele Mezzenga

    (ETH Zürich)

  • Ruedi Aebersold

    (ETH Zürich)

  • Alexander Leitner

    (ETH Zürich)

  • Maxim Yulikov

    (ETH Zürich)

  • Gunnar Jeschke

    (ETH Zürich)

  • Frédéric H.-T. Allain

    (ETH Zürich)

Abstract

RNA-binding proteins (RBPs) are crucial regulators of gene expression, often composed of defined domains interspersed with flexible, intrinsically disordered regions. Determining the structure of ribonucleoprotein (RNP) complexes involving such RBPs necessitates integrative structural modeling due to their lack of a single stable state. In this study, we integrate magnetic resonance, mass spectrometry, and small-angle scattering data to determine the solution structure of the polypyrimidine-tract binding protein 1 (PTBP1/hnRNP I) bound to an RNA fragment from the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). This binding, essential for enhancing the translation of viral RNA, leads to a complex structure that demonstrates RNA and protein compaction, while maintaining pronounced conformational flexibility. Acting as an RNA chaperone, PTBP1 orchestrates the IRES RNA into a few distinct conformations, exposing the RNA stems outward. This conformational diversity is likely common among RNP structures and functionally important. Our approach enables atomic-level characterization of heterogeneous RNP structures.

Suggested Citation

  • Georg Dorn & Christoph Gmeiner & Tebbe Vries & Emil Dedic & Mihajlo Novakovic & Fred F. Damberger & Christophe Maris & Esteban Finol & Chris P. Sarnowski & Joachim Kohlbrecher & Timothy J. Welsh & Sre, 2023. "Integrative solution structure of PTBP1-IRES complex reveals strong compaction and ordering with residual conformational flexibility," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42012-z
    DOI: 10.1038/s41467-023-42012-z
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    References listed on IDEAS

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