9QUN

apPol-nucleotide complex

Summary for 9QUN

• Entry DOI: 10.2210/pdb9qun/pdb
• EMDB information: 53379
• Descriptor: Plastid replication-repair enzyme, 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE (2 entities in total)
• Functional Keywords: dna polymerase, replication
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum)
• Total number of polymer chains: 1
• Total formula weight: 76980.66

Authors

Lahiri, I.,Kumari, A. (deposition date: 2025-04-10, release date: 2025-10-29)

Primary citation

Kumari, A.,Enache, T.,Craggs, T.D.,Pata, J.D.,Lahiri, I.
Structural basis of multitasking by the apicoplast DNA polymerase from Plasmodium falciparum.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: 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.

PubMed: 41099714
DOI: 10.1093/nar/gkaf1005

Experimental method

ELECTRON MICROSCOPY (3.9 Å)