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Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

Author

Listed:
  • Hauke S. Hillen

    (University Medical Center Goettingen
    University of Goettingen
    Max Planck Institute for Biophysical Chemistry)

  • Elena Lavdovskaia

    (University Medical Center Goettingen
    University of Goettingen)

  • Franziska Nadler

    (University Medical Center Goettingen)

  • Elisa Hanitsch

    (University Medical Center Goettingen)

  • Andreas Linden

    (Max Planck Institute for Biophysical Chemistry
    University Medical Center Goettingen)

  • Katherine E. Bohnsack

    (University Medical Center Goettingen)

  • Henning Urlaub

    (Max Planck Institute for Biophysical Chemistry
    University Medical Center Goettingen)

  • Ricarda Richter-Dennerlein

    (University Medical Center Goettingen
    University of Goettingen)

Abstract

Ribosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23702-y
    DOI: 10.1038/s41467-021-23702-y
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    Cited by:

    1. Bo Qin & Simon M. Lauer & Annika Balke & Carlos H. Vieira-Vieira & Jörg Bürger & Thorsten Mielke & Matthias Selbach & Patrick Scheerer & Christian M. T. Spahn & Rainer Nikolay, 2023. "Cryo-EM captures early ribosome assembly in action," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Franziska Nadler & Elena Lavdovskaia & Angelique Krempler & Luis Daniel Cruz-Zaragoza & Sven Dennerlein & Ricarda Richter-Dennerlein, 2022. "Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Miriam Cipullo & Genís Valentín Gesé & Shreekara Gopalakrishna & Annika Krueger & Vivian Lobo & Maria A. Pirozhkova & James Marks & Petra Páleníková & Dmitrii Shiriaev & Yong Liu & Jelena Misic & Yu C, 2024. "GTPBP8 plays a role in mitoribosome formation in human mitochondria," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Pedro Rebelo-Guiomar & Simone Pellegrino & Kyle C. Dent & Aldema Sas-Chen & Leonor Miller-Fleming & Caterina Garone & Lindsey Van Haute & Jack F. Rogan & Adam Dinan & Andrew E. Firth & Byron Andrews &, 2022. "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. 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.

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