IPIS3

IPIS3 (PBANKA_0623100) is a tryptophan-rich protein of Plasmodium berghei that contributes to the parasite-induced membrane compartments within infected host cells (PMID:36126089). It was identified as a co-precipitating partner of IBIS1 and localizes to intraerythrocytic P. berghei-induced membrane structures (IBIS) in infected red blood cells and to the parasitophorous vacuole membrane in liver-stage parasites (PMID:36126089). Gene deletion establishes that IPIS3 is required for efficient blood-stage parasite growth (PMID:36126089). Beyond this single study, no further mechanistic detail — including the biochemical basis of its association with IBIS1, its membrane-targeting determinants, or its molecular activity — has been characterized in the available corpus.

1. 2022 Medium

   The identity and functional role of proteins comprising P. berghei-induced membrane structures were incompletely defined; identifying IPIS3 as an IBIS1 partner established it as a component of these host-cell membrane compartments across both blood and liver stages, and gene deletion tied it to a fitness role.

   Evidence Co-immunoprecipitation with IBIS1, immunofluorescence localization, and gene deletion with blood-stage growth readout in P. berghei

   PMID:36126089

   Open questions at the time

   • The biochemical nature and stoichiometry of the IPIS3–IBIS1 association are not resolved (single lab study without structural or reconstitution data)
   • The membrane-targeting determinants and how IPIS3 reaches both the IBIS and the liver-stage parasitophorous vacuole membrane are unknown
   • The molecular activity of the tryptophan-rich domain and the mechanistic basis of the blood-stage growth defect are undefined

• It remains unknown what molecular function IPIS3 performs at these membrane structures and whether its role extends beyond structural complex membership to a defined biochemical activity.
• No molecular activity assigned to the tryptophan-rich domain
• No structural model of the IPIS3–IBIS1 complex
• Mechanism linking IPIS3 loss to reduced blood-stage growth unresolved