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-Structure paper
Title | Structural basis for late maturation steps of the human mitoribosomal large subunit. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 3673, Year 2021 |
Publish date | Jun 16, 2021 |
Authors | Miriam Cipullo / Genís Valentín Gesé / Anas Khawaja / B Martin Hällberg / Joanna Rorbach / |
PubMed Abstract | Mitochondrial ribosomes (mitoribosomes) synthesize a critical set of proteins essential for oxidative phosphorylation. Therefore, mitoribosomal function is vital to the cellular energy supply. ...Mitochondrial ribosomes (mitoribosomes) synthesize a critical set of proteins essential for oxidative phosphorylation. Therefore, mitoribosomal function is vital to the cellular energy supply. Mitoribosome biogenesis follows distinct molecular pathways that remain poorly understood. Here, we determine the cryo-EM structures of mitoribosomes isolated from human cell lines with either depleted or overexpressed mitoribosome assembly factor GTPBP5, allowing us to capture consecutive steps during mitoribosomal large subunit (mt-LSU) biogenesis. Our structures provide essential insights into the last steps of 16S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, which require the coordinated action of nine assembly factors. We show that mammalian-specific MTERF4 contributes to the folding of 16S rRNA, allowing 16 S rRNA methylation by MRM2, while GTPBP5 and NSUN4 promote fine-tuning rRNA rearrangements leading to PTC formation. Moreover, our data reveal an unexpected involvement of the elongation factor mtEF-Tu in mt-LSU assembly, where mtEF-Tu interacts with GTPBP5, similar to its interaction with tRNA during translational elongation. |
External links | Nat Commun / PubMed:34135318 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 - 3.2 Å |
Structure data | EMDB-12763, PDB-7o9k: EMDB-12764, PDB-7o9m: EMDB-12767: EMDB-12768: EMDB-12769: EMDB-12770: |
Chemicals | ChemComp-ZN: ChemComp-MG: ChemComp-SAM: ChemComp-GDP: ChemComp-GTP: ChemComp-SAH: ChemComp-PNS: |
Source |
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Keywords | RIBOSOME / Mitochondria / GTPase / Ribosome assembly intermediate |