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-Structure paper
| タイトル | Structural basis of multitasking by the apicoplast DNA polymerase from Plasmodium falciparum. |
|---|---|
| ジャーナル・号・ページ | Nucleic Acids Res, Vol. 53, Issue 19, Year 2025 |
| 掲載日 | 2025年10月14日 |
著者 | Anamika Kumari / Theodora Enache / Timothy D Craggs / Janice D Pata / Indrajit Lahiri / ![]() |
| PubMed 要旨 | Plasmodium falciparum is a eukaryotic pathogen responsible for the majority of malaria-related fatalities. Plasmodium belongs to the phylum Apicomplexa and, like most members of this phylum, contains ...Plasmodium falciparum is a eukaryotic pathogen responsible for the majority of malaria-related fatalities. Plasmodium belongs to the phylum Apicomplexa and, like most members of this phylum, contains a non-photosynthetic plastid called the apicoplast. The apicoplast has its own genome, replicated by a dedicated replisome. Unlike other cellular replisomes, the apicoplast replisome uses a single DNA polymerase (apPol). This suggests that apPol can multitask and catalyse both replicative and lesion bypass synthesis. Replicative synthesis relies on a restrictive active site for high accuracy while lesion bypass typically requires an open active site. This raises the question: how does apPol combine the structural features of multiple DNA polymerases in a single protein? Using single-particle electron cryomicroscopy (cryoEM), we have solved the structures of apPol bound to its undamaged DNA and nucleotide substrates in five pre-chemistry conformational states. We found that apPol can accommodate a nascent base pair with the fingers in an open configuration, which might facilitate the lesion bypass activity. In the fingers-open state, we identified a nascent base pair checkpoint that preferentially selects Watson-Crick base pairs, an essential requirement for replicative synthesis. Taken together, these structural features might explain how apPol balances replicative and lesion bypass synthesis. |
リンク | Nucleic Acids Res / PubMed:41099714 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.2 - 4.2 Å |
| 構造データ | EMDB-53335, PDB-9qsc: EMDB-53374, PDB-9qu8: EMDB-53376, PDB-9qua: EMDB-53378, PDB-9quj: EMDB-53379, PDB-9qun: EMDB-53391, PDB-9qv9: |
| 化合物 | ![]() ChemComp-DGT: ![]() ChemComp-CA: |
| 由来 |
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キーワード | REPLICATION / DNA polymerase |
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