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Title | The Giardia lamblia ribosome structure reveals divergence in several biological pathways and the mode of emetine function. |
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Journal, issue, pages | Structure, Vol. 32, Issue 4, Page 400-410.e4, Year 2024 |
Publish date | Apr 4, 2024 |
Authors | Daniel R Eiler / Brian T Wimberly / Danielle Y Bilodeau / J Matthew Taliaferro / Philip Reigan / Olivia S Rissland / Jeffrey S Kieft / |
PubMed Abstract | 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 ...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 links | Structure / PubMed:38242118 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.49 - 3.24 Å |
Structure data | EMDB-29407, PDB-8fru: EMDB-29495, PDB-8fvy: EMDB-29721, PDB-8g4i: EMDB-29730, PDB-8g4s: EMDB-29897: Focused refinement of the 40S subunit head of the 80S Giardia lamblia ribosome at 2.94 angstroms resolution. EMDB-29906: 80S Giardia lamblia ribosome at 2.66 angstroms resolution with Emetine in the the V1 conformation EMDB-29918: 80S Giardia lamblia ribosome at 2.67 angstroms resolution with Emetine in the the V2 conformation |
Chemicals | ChemComp-K: ChemComp-MG: ChemComp-ZN: ChemComp-NA: ChemComp-SPD: ChemComp-HOH: ChemComp-YAT: |
Source |
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Keywords | RIBOSOME / Giardia lamblia / Ribosome structure / Translation / parasite |