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TitleThe structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateJun 6, 2024
AuthorsSamuel Holvec / Charles Barchet / Antony Lechner / Léo Fréchin / S Nimali T De Silva / Isabelle Hazemann / Philippe Wolff / Ottilie von Loeffelholz / Bruno P Klaholz /
PubMed AbstractThe 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 linksNat Struct Mol Biol / PubMed:38844527
MethodsEM (single particle)
Resolution1.9 - 2.22 Å
Structure data

18539

8qoi

EMDB-18539, PDB-8qoi:
Structure of the human 80S ribosome at 1.9 A resolution - the molecular role of chemical modifications and ions in RNA
Method: EM (single particle) / Resolution: 1.9 Å

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
Method: EM (single particle) / Resolution: 1.9 Å

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
Method: EM (single particle) / Resolution: 2.0 Å

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
Method: EM (single particle) / Resolution: 1.9 Å

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.
Method: EM (single particle) / Resolution: 2.22 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-SPD:
SPERMIDINE

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsRIBOSOME / cryo-electron microscopie / post-transcriptional modifications

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