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Title | The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 31, Issue 8, Page 1251-1264, Year 2024 |
Publish date | Jun 6, 2024 |
Authors | Samuel Holvec / Charles Barchet / Antony Lechner / Léo Fréchin / S Nimali T De Silva / Isabelle Hazemann / Philippe Wolff / Ottilie von Loeffelholz / Bruno P Klaholz / |
PubMed Abstract | The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. Here we present the 1.9 Å resolution cryo ...The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. Here we present the 1.9 Å resolution cryo electron microscopy structure of the 80S human ribosome resolving numerous new ribosomal RNA modifications and functionally important ions such as Zn, K and Mg, including their associated individual water molecules. The 2'-O-methylation, pseudo-uridine and base modifications were confirmed by mass spectrometry, resulting in a complete investigation of the >230 sites, many of which could not be addressed previously. They choreograph key interactions within the RNA and at the interface with proteins, including at the ribosomal subunit interfaces of the fully assembled 80S ribosome. Uridine isomerization turns out to be a key mechanism for U-A base pair stabilization in RNA in general. The structural environment of chemical modifications and ions is primordial for the RNA architecture of the mature human ribosome, hence providing a structural framework to address their role in healthy states and in human diseases. |
External links | Nat Struct Mol Biol / PubMed:38844527 |
Methods | EM (single particle) |
Resolution | 1.9 - 2.22 Å |
Structure data | EMDB-18539, PDB-8qoi: EMDB-18812: The structure of the human 80S ribosome at 1.9 angstrom resolution reveals the molecular role of chemical modifications and ions in RNA - Focused refinement of the of the 60S subunit EMDB-18813: The structure of the human 80S ribosome at 1.9 angstrom resolution reveals the molecular role of chemical modifications and ions in RNA - Focused refinement of the of the 40S subunit body EMDB-18814: The structure of the human 80S ribosome at 1.9 angstrom resolution reveals the molecular role of chemical modifications and ions in RNA - Focused refinement of the of the 40S subunit head EMDB-18815: Structure of the human 80S ribosome at 1.9 A resolution - the molecular role of chemical modifications and ions in RNA - Global human 80S ribosome refinement before focused refinements. |
Chemicals | ChemComp-MG: ChemComp-K: ChemComp-SPD: ChemComp-ZN: ChemComp-HOH: |
Source |
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Keywords | RIBOSOME / cryo-electron microscopie / post-transcriptional modifications |