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TitleThe Giardia lamblia ribosome structure reveals divergence in several biological pathways and the mode of emetine function.
Journal, issue, pagesStructure, Vol. 32, Issue 4, Page 400-410.e4, Year 2024
Publish dateApr 4, 2024
AuthorsDaniel R Eiler / Brian T Wimberly / Danielle Y Bilodeau / J Matthew Taliaferro / Philip Reigan / Olivia S Rissland / Jeffrey S Kieft /
PubMed AbstractGiardia lamblia is a deeply branching protist and a human pathogen. Its unusual biology presents the opportunity to explore conserved and fundamental molecular mechanisms. We determined the structure ...Giardia lamblia is a deeply branching protist and a human pathogen. Its unusual biology presents the opportunity to explore conserved and fundamental molecular mechanisms. We determined the structure of the G. lamblia 80S ribosome bound to tRNA, mRNA, and the antibiotic emetine by cryo-electron microscopy, to an overall resolution of 2.49 Å. The structure reveals rapidly evolving protein and nucleotide regions, differences in the peptide exit tunnel, and likely altered ribosome quality control pathways. Examination of translation initiation factor binding sites suggests these interactions are conserved despite a divergent initiation mechanism. Highlighting the potential of G. lamblia to resolve conserved biological principles; our structure reveals the interactions of the translation inhibitor emetine with the ribosome and mRNA, thus providing insight into the mechanism of action for this widely used antibiotic. Our work defines key questions in G. lamblia and motivates future experiments to explore the diversity of eukaryotic gene regulation.
External linksStructure / PubMed:38242118 / PubMed Central
MethodsEM (single particle)
Resolution2.49 - 3.14 Å
Structure data

29407

8fru

EMDB-29407, PDB-8fru:
60S subunit of the Giardia lamblia 80S ribosome
Method: EM (single particle) / Resolution: 2.49 Å

29495

8fvy

EMDB-29495, PDB-8fvy:
40S subunit of the Giardia lamblia 80S ribosome
Method: EM (single particle) / Resolution: 2.94 Å

29730

8g4s

EMDB-29730, PDB-8g4s:
40S ribosomal subunit of the 80S Giardia intestinalis assemblage A ribosome with Emetine bound in V2 conformation with mRNA and three tRNAs.
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-29918: 80S Giardia lamblia ribosome at 2.67 angstroms resolution with Emetine in the the V2 conformation
Method: EM (single particle) / Resolution: 2.67 Å

Chemicals

ChemComp-K:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-SPD:
SPERMIDINE / Spermidine

ChemComp-HOH:
WATER / Water

ChemComp-YAT:
emetine

Source
  • giardia intestinalis assemblage a (eukaryote)
KeywordsRIBOSOME / Giardia lamblia / Ribosome structure / Translation / parasite

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