National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM118070
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI149210
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM128680
米国
引用
ジャーナル: Structure / 年: 2024 タイトル: The Giardia lamblia ribosome structure reveals divergence in several biological pathways and the mode of emetine function. 著者: Daniel R Eiler / Brian T Wimberly / Danielle Y Bilodeau / J Matthew Taliaferro / Philip Reigan / Olivia S Rissland / Jeffrey S Kieft / 要旨: 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.