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Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk.
- Source :
-
Nature communications [Nat Commun] 2024 May 20; Vol. 15 (1), pp. 4272. Date of Electronic Publication: 2024 May 20. - Publication Year :
- 2024
-
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-tRNA <superscript>Val</superscript> . 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Ligands
Molecular Dynamics Simulation
RNA, Messenger metabolism
RNA, Messenger genetics
Mitochondria metabolism
RNA, Ribosomal metabolism
RNA, Ribosomal chemistry
Ribosomal Proteins metabolism
Ribosomal Proteins chemistry
Guanosine Diphosphate metabolism
Polyamines metabolism
Polyamines chemistry
Protein Binding
RNA, Transfer metabolism
RNA, Transfer chemistry
RNA, Transfer genetics
Mitochondrial Ribosomes metabolism
Mitochondrial Ribosomes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38769321
- Full Text :
- https://doi.org/10.1038/s41467-024-48163-x