HOP

PfHop (HOP/PF3D7_1434300) is a stress-inducible adaptor protein that bridges the two major cytosolic chaperones of Plasmodium falciparum, PfHsp70-1 and PfHsp90, within a functional complex in trophozoite-stage parasites (PMID:22005844, PMID:26267894). It co-localizes with both chaperones and co-fractionates with them, and it uses distinct TPR subdomains to engage each partner: the TPR1 and TPR2B subdomains bind the C-terminus of PfHsp70-1 while the TPR2A motif binds the C-terminus of PfHsp90 (PMID:26267894). The PfHop–PfHsp70-1 association is nucleotide-dependent, favored by the ADP-bound state of Hsp70, and PfHop can self-associate, consistent with a scaffolding role that assembles the chaperone complex (PMID:26267894). Beyond this adaptor function, no further mechanistic role for PF3D7_1434300 has been characterized in the available corpus.

1. 2011 Medium

   Establishing whether P. falciparum possesses a physical link between its two principal chaperones addressed whether Hsp70 and Hsp90 could act coordinately; the finding placed PfHop in a complex with both.

   Evidence Recombinant protein production with anti-PfHop antisera, immunofluorescence co-localization, gel filtration and co-immunoprecipitation in trophozoite-stage parasites

   PMID:22005844

   Open questions at the time

   • Interaction shown at the complex level without direct binding measurement or defined interfaces
   • No mutagenesis or in vitro reconstitution to prove PfHop is the bridging factor
   • Functional consequence for parasite biology not tested
2. 2015 High

   The prior complex-level observation left open how PfHop engages each chaperone; mapping subdomain-specific, nucleotide-dependent binding established PfHop as a direct scaffold with defined interfaces.

   Evidence Far Western, surface plasmon resonance, co-immunoprecipitation, split-GFP subdomain-binding assays, and size exclusion chromatography

   PMID:26267894

   Open questions at the time

   • No structural model of the assembled PfHop–PfHsp70-1–PfHsp90 complex
   • Functional/client-processing consequences of the interaction not demonstrated
   • In vivo requirement of PfHop for parasite viability or stress survival untested
3. 2018 Low

   Whether Hop-type proteins recognize a conserved Hsp70 C-terminal motif was tested using human Hop against PfHsp70-x, implying the interface through which Hop proteins engage Hsp70 partners in P. falciparum.

   Evidence Recombinant protein biochemistry and in vitro binding assays between the PfHsp70-x EEVN motif and human Hop (not PfHop itself)

   PMID:30183110

   Open questions at the time

   • Used human Hop, not PfHop/PF3D7_1434300, so the inference for this gene is indirect
   • Did not test PfHop binding to PfHsp70-x directly
   • Single in vitro binding assay without cellular validation

• The functional consequences of PfHop-mediated chaperone assembly for parasite growth, stress survival, and client protein maturation remain unaddressed.
• No loss-of-function or knockdown phenotype for PF3D7_1434300
• No identified chaperone clients dependent on PfHop
• No structural model of the ternary complex