Journal article
Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug
Nature structural & molecular biology, v 32(11), pp 2158-2164
18 Aug 2025
PMID: 40825879
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Our understanding of cellular events is hampered by the gap between the resolution at which we can observe events inside cells and our ability to replicate physiological conditions in test tubes. Here, we show in Plasmodium falciparum, a non-model organism of high medical importance, that this gap can be bridged by using an integrated structural biology approach to visualize events inside the cell at molecular resolution. We determined eight high-resolution structures of the native malarial ribosome in actively translating states inside P. falciparum-infected human erythrocytes using in situ cryo-electron tomography. Following perturbation with a Plasmodium-specific translation inhibitor, we then observed a decrease in elongation factor-bound ribosomal states and an apparent upregulation of ribosome biogenesis in inhibitor-treated parasites. Our work elucidates new molecular details of the malarial translation elongation cycle and demonstrates direct multiscale visualization of drug-induced phenotypic changes in the structure and localization of individual molecules within the native cellular context.
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Details
- Title
- Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug
- Creators
- Leonie Anton - Columbia University Irving Medical CenterWenjing Cheng - Columbia University Irving Medical CenterMeseret T Haile - Columbia University Irving Medical CenterJerzy M Dziekan - Walter and Eliza Hall Institute of Medical ResearchDavid W Cobb - Columbia University Irving Medical CenterXiyan Zhu - Columbia University Irving Medical CenterLeyan Han - Columbia University Irving Medical CenterEmerson Li - Columbia University Irving Medical CenterAnjali Nair - Columbia University Irving Medical CenterCarolyn L Lee - Columbia University Irving Medical CenterHanyu Wang - Columbia University Irving Medical CenterHangjun Ke - Drexel University, Microbiology and ImmunologyGuoan Zhang - Weill Cornell MedicineEmma H Doud - Indiana University School of Medicine - LafayetteAlan F Cowman - The University of MelbourneChi-Min Ho - Columbia University Irving Medical Center
- Publication Details
- Nature structural & molecular biology, v 32(11), pp 2158-2164
- Grant note
- DP5 OD029613 / NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001551764700001
- Scopus ID
- 2-s2.0-105013570131
- Other Identifier
- 991022084049004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology