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Title | Distinct pre-initiation steps in human mitochondrial translation. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 2932, Year 2020 |
Publish date | Jun 10, 2020 |
Authors | Anas Khawaja / Yuzuru Itoh / Cristina Remes / Henrik Spåhr / Olessya Yukhnovets / Henning Höfig / Alexey Amunts / Joanna Rorbach / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:32522994 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.85 - 3.38 Å |
Structure data | EMDB-10021, PDB-6rw4: EMDB-10022, PDB-6rw5: EMDB-10023: EMDB-10024: EMDB-10025: EMDB-10026: EMDB-10027: EMDB-10028: EMDB-10029: EMDB-10030: EMDB-10031: EMDB-10032: |
Chemicals | ChemComp-NAD: ChemComp-SPM: ChemComp-SRY: ChemComp-MG: ChemComp-K: ChemComp-ZN: ChemComp-FES: ChemComp-ATP: ChemComp-GNP: ChemComp-HOH: |
Source |
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Keywords | RIBOSOME / ribosomal small subunit / initiation complex / initiation factor 3 / mitochondria / initiation factor |