Toxoplasma gondii aspartyl protease 3

ABSTRACT: The micronemes and rhoptries are specialized organelles that secrete their contents at the apical tip of apicomplexan parasites in a sequential and regulated manner. Microneme and rhoptry proteins crucially participate in motility, invasion, and egress from infected cells. They first traffic through an endosomal-like compartment (ELC) and are subjected to proteolytic maturation prior to organellar storage and discharge. Here we establish that Toxoplasma gondii aspartyl protease 3 (ASP3) resides in the ELC and plays a crucial role associated to rhoptry discharge during invasion and to host cell plasma membrane lysis during egress. A comparison of the N-terminome, by terminal amine isotopic labelling of substrates (TAILS) between wild type and ASP3 depleted parasites identified microneme and rhoptry proteins as putative ASP3 substrates. The role of ASP3 as maturase for known as well as newly identified organellar proteins is confirmed in vivo and in vitro. A derivative from a series of antimalarial compounds based on a hydroxyethylamine scaffold interrupts the lytic cycle of T. gondii at submicromolar concentration by selectively targeting ASP3.

INSTRUMENT(S):

ORGANISM(S): Toxoplasma Gondii

SUBMITTER: Tobias Kockmann  

LAB HEAD: Adrian B. Hehl

PROVIDER: PXD006235 | Pride | 2018-01-30

REPOSITORIES: Pride