Distinct pre-initiation steps in human mitochondrial translation
Nature Communications, vol. 11, pp. 2932
Abstract
Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.
Authors 8
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Affiliation as printed
Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65, Solna, Sweden
Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden
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Stockholm University · Science for Life Laboratory · Karolinska Institutet
Affiliation as printed
Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65, Solna, Sweden
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden
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Max Planck Institute for Biology of Ageing
Affiliation as printed
Department of Mitochondrial Biology, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany
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Karolinska Institutet · Max Planck Institute for Biology of Ageing
Affiliation as printed
Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65, Solna, Sweden
Department of Mitochondrial Biology, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany
Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Forschungszentrum Jülich, Institute of Complex Systems ICS-5, Jülich, Germany
RWTH Aachen, I. Physikalisches Institut (IA), Aachen, Germany
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Forschungszentrum Jülich, Institute of Complex Systems ICS-5, Jülich, Germany
RWTH Aachen, I. Physikalisches Institut (IA), Aachen, Germany
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Alexey Amunts corresponding
Stockholm University · Science for Life Laboratory · Karolinska Institutet
Affiliation as printed
Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65, Solna, Sweden. amunts@scilifelab.se
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden. amunts@scilifelab.se
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden
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Joanna Rorbach corresponding
Affiliation as printed
Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65, Solna, Sweden. joanna.rorbach@ki.se
Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden. joanna.rorbach@ki.se
Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden
Cited by 81 stored of 81
Cited by patents worldwide 1 (Lens.org)
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TRIGGER-ASSEMBLED MEMBRANE-SPANNING NUCLEIC ACID NANOSTRUCTURESWO2023166222A1 2023-09-07 Pending