Inhibition of the assembly of <i>Plasmodium</i> Hsp70-1 and Hsp40 complex blocks DNA replication by destabilizing ribonucleotide reductase subunit-2.

ABSTRACT: Plasmodium falciparum undergoes endoreduplication, in which its nuclear, mitochondrial, and apicoplast genomes are replicated multiple times without cytokinesis,; enabling replication as a promising target for arresting parasite growth and pathogenicity. Previously, it was reported that the inhibition of expression of small subunit of ribonucleotide reductase (PfR2) leads to the inhibition of DNA synthesis and growth of the parasites. Here, we report the molecular determinant that is necessary for aiding early folding intermediates of PfR2. We find that PfR2 interacts with the cytosolic Type-I Hsp40-cochaperone PfYdj1 (Pf3D7_1437900), which subsequently interacts with PfHsp70-1 through its Histidine-Proline-Aspartate (HPD) motif. Such association of PfR2 is specific toward PfYdj1 an

SUBMITTER: Alkhatib I 

PROVIDER: S-EPMC12505967 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature