A recombinant expression system for the <i>Plasmodium falciparum</i> proteasome enables structural analysis of its assembly and the design of selective inhibitors.

ABSTRACT: The Plasmodium falciparum 20S proteasome (Pf20S) has emerged as a promising antimalarial target. Development of therapeutics to this target has previously relied on native purifications of Pf20S, which is challenging and has limited the scope of previous efforts. Here, we report an effective recombinant Pf20S platform to facilitate drug discovery. Proteasome assembly was carried out in insect cells by co-expressing all fourteen subunits along with the essential chaperone homolog, Ump1. Unexpectedly, the isolated proteins consisted of both a mature and an immature complex. Cryo-EM analysis of the immature complexes revealed structural insights detailing how Ump1 and the propeptides of the β2 and β5 subunits coordinate β-ring assembly, which differ from human and yeast homologs. Bioch

SUBMITTER: Fajtova P 

PROVIDER: S-EPMC12363949 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature