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| Title | Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 32, Issue 11, Page 2158-2164, Year 2025 |
| Publish date | Aug 18, 2025 |
Authors | Leonie Anton / Wenjing Cheng / Meseret T Haile / Jerzy M Dziekan / David W Cobb / Xiyan Zhu / Leyan Han / Emerson Li / Anjali Nair / Carolyn L Lee / Hanyu Wang / Hangjun Ke / Guoan Zhang / Emma H Doud / Alan F Cowman / Chi-Min Ho / ![]() |
| PubMed 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. ...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. |
External links | Nat Struct Mol Biol / PubMed:40825879 / PubMed Central |
| Methods | EM (subtomogram averaging) / EM (single particle) |
| Resolution | 2.3 - 18.0 Å |
| Structure data | EMDB-41485, PDB-8tpu: ![]() EMDB-41486: Subtomogram averaged decoding-1 state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41487: Subtomogram averaged decoding-2 state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41488: Subtomogram averaged classical iPRE state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41489: Subtomogram averaged rotated-1 PRE state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41490: Subtomogram averaged rotated-2 PRE state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41491: Subtomogram averaged translocation state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41492: Subtomogram averaged POST state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41493: Subtomogram averaged unloaded state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-41494: Subtomogram averaged non-rotated 80S ribosome of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-42209: Subtomogram averaged rotated-1 PRE back rolled state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-42210: Subtomogram averaged eEF1alpha hibernating state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes ![]() EMDB-42211: Subtomogram averaged eEF2 hibernating-1 state of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes EMDB-44915, PDB-9bup: EMDB-44916, PDB-9buq: EMDB-44918, PDB-9bus: EMDB-44919, PDB-9but: EMDB-44920, PDB-9buu: |
| Source |
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Keywords | RIBOSOME / malaria / cryoET / in situ / Plasmodium falciparum / translation / cryoEM / single particle |
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