Fig. 1

Host-driven targeted degradation of a Plasmodium liver stage PVM protein using HaloTag technology. The illustration shows: (1) the host cytosol-exposed C-terminus of the PVM protein UIS4 fused to HaloTag (HT), (2) the binding of the reactive chloroalkane HaloTag ligand (HTL) moiety of a HaloPROTAC to the UIS4-HT fusion protein, (3) the binding of a host E3 ligase to the E3 ligase ligand moiety on the same HaloPROTAC, and (4) the ubiquitination and (5) the proteasomal degradation of UIS4-HT. PVM, parasitophorous vacuole membrane; PPM, parasite plasma membrane; Ub, ubiquitin; HaloPROTAC, HaloTag-targeted proteolysis targeting chimeras.