GET3

PF3D7_0415000 (GET3) is the Plasmodium falciparum homolog of the GET3 ATPase and functions as a component of a conserved Guided Entry of Tail-Anchored (GET) pathway complex that mediates post-translational membrane insertion of tail-anchored (TA) proteins in the parasite (PMID:34780541). Proximity labelling identified an association between GET3 and a subset of predicted TA proteins, and in vitro association assays validated direct interactions with the P. falciparum homologs of Get4 and Get2, placing GET3 within a multi-subunit targeting complex (PMID:34780541). Beyond this membership in the GET complex and its association with candidate TA-protein clients (PMID:34780541), no further mechanistic detail — including catalytic activity, structure, or the specific membranes targeted — has been characterized in the available corpus.

1. 2021 Medium

   It was unknown whether P. falciparum possesses a functional GET pathway; this work established GET3 as the parasite's GET3 homolog operating within a conserved complex for tail-anchored protein targeting.

   Evidence Proximity labelling (BioID) identifying associated TA proteins plus in vitro association/pulldown assays confirming binding to the Get4 and Get2 homologs, in P. falciparum

   PMID:34780541

   Open questions at the time

   • No mutagenesis or structural validation of the interactions
   • ATPase activity of GET3 not demonstrated biochemically
   • The specific TA-protein clients and target membranes not functionally confirmed

• Whether GET3's ATPase activity, its structural mechanism of TA-protein capture and release, and the essentiality of the pathway for parasite viability remain uncharacterized.
• No enzymatic characterization of the ATPase cycle
• No structural model of GET3 or its complex
• No loss-of-function phenotype in the parasite