ausblenden:
Schlagwörter:
-
Zusammenfassung:
In eukaryotic cells, the ubiquitin-proteasome system as a key regulator of protein quality control is
an excellent drug target. We therefore aimed to analyze the 26S proteasome complex in the malaria
parasite Plasmodium falciparum, which still threatens almost half of the world’s population. First, we
established an affinity purification protocol allowing for the isolation of functional 26S proteasome
complexes from the parasite. Subunit composition of the proteasome and component stoichiometry
were studied and physiologic interacting partners were identified via in situ protein crosslinking.
Furthermore, intrinsic ubiquitin receptors of the plasmodial proteasome were determined and their
roles in proteasomal substrate recognition were analyzed. Notably, PfUSP14 was characterized
as a proteasome-associated deubiquitinase resulting in the concept that targeting proteasomal
deubiquitinating activity in P. falciparum may represent a promising antimalarial strategy. The data
provide insights into a profound network orchestrated by the plasmodial proteasome and identified
novel drug target candidates in the ubiquitin-proteasome system.
