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Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk

Author

Listed:
  • Vivek Singh

    (Stockholm University)

  • Yuzuru Itoh

    (Stockholm University
    University of Tokyo)

  • Samuel Del’Olio

    (University of Miami Miller School of Medicine)

  • Asem Hassan

    (Northeastern University
    Northeastern University)

  • Andreas Naschberger

    (Stockholm University
    King Abdullah University of Science and Technology)

  • Rasmus Kock Flygaard

    (Aarhus University)

  • Yuko Nobe

    (Tokyo Metropolitan University)

  • Keiichi Izumikawa

    (Meiji Pharmaceutical University)

  • Shintaro Aibara

    (Stockholm University)

  • Juni Andréll

    (Karolinska Institutet)

  • Paul C. Whitford

    (Northeastern University
    Northeastern University)

  • Antoni Barrientos

    (University of Miami Miller School of Medicine
    University of Miami Miller School of Medicine
    University of Miami Miller School of Medicine)

  • Masato Taoka

    (Tokyo Metropolitan University)

  • Alexey Amunts

    (Stockholm University
    Westlake University)

Abstract

The mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 Å resolution structure of human mitoribosome together with validated mitoribosomal RNA (rRNA) modifications, including aminoacylated CP-tRNAVal. The structure shows how mitoribosomal proteins stabilise binding of mRNA and tRNA helping to align it in the decoding center, whereas the GDP-bound mS29 stabilizes intersubunit communication. Comparison between different states, with respect to tRNA position, allowed us to characterize a non-canonical L1 stalk, and molecular dynamics simulations revealed how it facilitates tRNA transitions in a way that does not require interactions with rRNA. We also report functionally important polyamines that are depleted when cells are subjected to an antibiotic treatment. The structural, biochemical, and computational data illuminate the principal functional components of the translation mechanism in mitochondria and provide a description of the structure and function of the human mitoribosome.

Suggested Citation

  • Vivek Singh & Yuzuru Itoh & Samuel Del’Olio & Asem Hassan & Andreas Naschberger & Rasmus Kock Flygaard & Yuko Nobe & Keiichi Izumikawa & Shintaro Aibara & Juni Andréll & Paul C. Whitford & Antoni Barr, 2024. "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48163-x
    DOI: 10.1038/s41467-024-48163-x
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    References listed on IDEAS

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