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-Structure paper
| タイトル | Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug. |
|---|---|
| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 32, Issue 11, Page 2158-2164, Year 2025 |
| 掲載日 | 2025年8月18日 |
 著者 | 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 要旨 | 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. |
 リンク | Nat Struct Mol Biol / PubMed:40825879 / PubMed Central |
| 手法 | EM (サブトモグラム平均) / EM (単粒子) |
| 解像度 | 2.3 - 18.0 Å |
| 構造データ | 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: |
| 由来 |
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 キーワード | RIBOSOME / malaria / cryoET / in situ / Plasmodium falciparum / translation / cryoEM / single particle |
plasmodium falciparum 3d7 (マラリア病原虫)