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TitleCryoEM structures of pseudouridine-free ribosome suggest impacts of chemical modifications on ribosome conformations.
Journal, issue, pagesStructure, Vol. 30, Issue 7, Page 983-992.e5, Year 2022
Publish dateJul 7, 2022
AuthorsYu Zhao / Jay Rai / Hongguo Yu / Hong Li /
PubMed AbstractPseudouridine, the most abundant form of RNA modification, is known to play important roles in ribosome function. Mutations in human DKC1, the pseudouridine synthase responsible for catalyzing the ...Pseudouridine, the most abundant form of RNA modification, is known to play important roles in ribosome function. Mutations in human DKC1, the pseudouridine synthase responsible for catalyzing the ribosome RNA modification, cause translation deficiencies and are associated with a complex cancer predisposition. The structural basis for how pseudouridine impacts ribosome function remains uncharacterized. Here, we characterized structures and conformations of a fully modified and a pseudouridine-free ribosome from Saccharomyces cerevisiae in the absence of ligands or when bound with translocation inhibitor cycloheximide by electron cryomicroscopy. In the modified ribosome, the rearranged N1 atom of pseudouridine is observed to stabilize key functional motifs by establishing predominately water-mediated close contacts with the phosphate backbone. The pseudouridine-free ribosome, however, is devoid of such interactions and displays conformations reflective of abnormal inter-subunit movements. The erroneous motions of the pseudouridine-free ribosome may explain its observed deficiencies in translation.
External linksStructure / PubMed:35489333 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.05 Å
Structure data

EMDB-23934, PDB-7mpi:
Stm1 bound vacant 80S structure isolated from cbf5-D95A
Method: EM (single particle) / Resolution: 3.05 Å

EMDB-23935, PDB-7mpj:
Stm1 bound vacant 80S structure isolated from wild-type
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-24235, PDB-7n8b:
Cycloheximide bound vacant 80S structure isolated from cbf5-D95A
Method: EM (single particle) / Resolution: 3.05 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-3HE:
4-{(2R)-2-[(1S,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl}piperidine-2,6-dione

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • Baker's Yeast (brewer's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsRIBOSOME / yeast / 80S complex / chemical modification

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