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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

    as
    1. Yuzuru Itoh & Anas Khawaja & Ivan Laptev & Miriam Cipullo & Ilian Atanassov & Petr Sergiev & Joanna Rorbach & Alexey Amunts, 2022. "Mechanism of mitoribosomal small subunit biogenesis and preinitiation," Nature, Nature, vol. 606(7914), pages 603-608, June.
    2. Alexey Rozov & Iskander Khusainov & Kamel El Omari & Ramona Duman & Vitaliy Mykhaylyk & Marat Yusupov & Eric Westhof & Armin Wagner & Gulnara Yusupova, 2019. "Importance of potassium ions for ribosome structure and function revealed by long-wavelength X-ray diffraction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Takeo Suzuki & Yuka Yashiro & Ittoku Kikuchi & Yuma Ishigami & Hironori Saito & Ikuya Matsuzawa & Shunpei Okada & Mari Mito & Shintaro Iwasaki & Ding Ma & Xuewei Zhao & Kana Asano & Huan Lin & Yohei K, 2020. "Complete chemical structures of human mitochondrial tRNAs," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    4. Georg K. A. Hochberg & Yang Liu & Erik G. Marklund & Brian P. H. Metzger & Arthur Laganowsky & Joseph W. Thornton, 2020. "A hydrophobic ratchet entrenches molecular complexes," Nature, Nature, vol. 588(7838), pages 503-508, December.
    5. Nathan J. Harper & Chloe Burnside & Sebastian Klinge, 2023. "Principles of mitoribosomal small subunit assembly in eukaryotes," Nature, Nature, vol. 614(7946), pages 175-181, February.
    6. Mariana Levi & Kelsey Walak & Ailun Wang & Udayan Mohanty & Paul C. Whitford, 2020. "A steric gate controls P/E hybrid-state formation of tRNA on the ribosome," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    7. Ravi Kiran Koripella & Manjuli R. Sharma & Kalpana Bhargava & Partha P. Datta & Prem S. Kaushal & Pooja Keshavan & Linda L. Spremulli & Nilesh K. Banavali & Rajendra K. Agrawal, 2020. "Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    8. Christopher B. Medina & Parul Mehrotra & Sanja Arandjelovic & Justin S. A. Perry & Yizhan Guo & Sho Morioka & Brady Barron & Scott F. Walk & Bart Ghesquière & Alexander S. Krupnick & Ulrike Lorenz & K, 2020. "Metabolites released from apoptotic cells act as tissue messengers," Nature, Nature, vol. 580(7801), pages 130-135, April.
    9. Hauke S. Hillen & Elena Lavdovskaia & Franziska Nadler & Elisa Hanitsch & Andreas Linden & Katherine E. Bohnsack & Henning Urlaub & Ricarda Richter-Dennerlein, 2021. "Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    10. Kien Nguyen & Paul C. Whitford, 2016. "Steric interactions lead to collective tilting motion in the ribosome during mRNA–tRNA translocation," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    11. Anas Khawaja & Yuzuru Itoh & Cristina Remes & Henrik Spåhr & Olessya Yukhnovets & Henning Höfig & Alexey Amunts & Joanna Rorbach, 2020. "Distinct pre-initiation steps in human mitochondrial translation," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    12. Basil J. Greber & Daniel Boehringer & Marc Leibundgut & Philipp Bieri & Alexander Leitner & Nikolaus Schmitz & Ruedi Aebersold & Nenad Ban, 2014. "The complete structure of the large subunit of the mammalian mitochondrial ribosome," Nature, Nature, vol. 515(7526), pages 283-286, November.
    13. Eva Kummer & Marc Leibundgut & Oliver Rackham & Richard G. Lee & Daniel Boehringer & Aleksandra Filipovska & Nenad Ban, 2018. "Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM," Nature, Nature, vol. 560(7717), pages 263-267, August.
    14. Yuzuru Itoh & Andreas Naschberger & Narges Mortezaei & Johannes M. Herrmann & Alexey Amunts, 2020. "Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    15. Miriam Cipullo & Genís Valentín Gesé & Anas Khawaja & B. Martin Hällberg & Joanna Rorbach, 2021. "Structural basis for late maturation steps of the human mitoribosomal large subunit," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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