PF3D7_0927000

PF3D7_0927000 (p23) is a co-chaperone of the P. falciparum Hsp90 (PfHsp90) chaperone machinery that also possesses intrinsic, Hsp90-independent chaperone activity, suppressing thermal aggregation of model substrates such as citrate synthase in vitro (PMID:20140477, PMID:29191421). It binds PfHsp90 directly and inhibits its ATPase activity, with binding mediated by residues K91, H93, W94, and K96 identified through model-guided mutagenesis (PMID:20140477). p23 engages the same region of PfHsp90 as the co-chaperone PfAha1 and competes with it for binding in an MgCl2- and ATP-dependent manner, positioning p23 as a regulator of the composition and cycling of the PfHsp90 multichaperone complex (PMID:22100910). The P. falciparum genome encodes two divergent p23 proteins, Pfp23A (PF3D7_0927000) and Pfp23B, sharing only ~13% identity; both behave as elongated monomers in solution, display intrinsic chaperone activity, and inhibit PfHsp90 ATPase activity, with Pfp23A being the more thermally and chemically stable of the two (PMID:29191421). Beyond these in vitro biochemical properties, the cellular and parasite-stage functions of PF3D7_0927000 have not been characterized in the available corpus.

1. 2010 Medium

   Establishing whether the parasite p23 homolog is a functional chaperone and Hsp90 partner, this work showed recombinant Pfp23 both suppresses substrate aggregation on its own and binds PfHsp90 while inhibiting its ATPase activity, defining it as a bona fide co-chaperone with intrinsic activity.

   Evidence In vitro aggregation suppression, protein-protein interaction, and ATPase assays with recombinant proteins

   PMID:20140477

   Open questions at the time

   • Single lab, in vitro reconstitution only; no cellular or parasite-based validation
   • No structural determination of the interaction
2. 2010 Medium

   To localize the interaction interface, model-guided mutagenesis pinpointed Pfp23 residues K91, H93, W94, and K96 as required for PfHsp90 binding, giving a residue-level map of the co-chaperone contact.

   Evidence Homology modeling of the Pfp23-PfHsp90 complex with site-directed mutagenesis

   PMID:20140477

   Open questions at the time

   • Interface inferred from a homology model, not a crystal or cryo-EM structure
   • Contribution of PfHsp90-side residues not defined
3. 2011 Medium

   Addressing how p23 fits within the wider co-chaperone network, competition pull-downs showed Pfp23 competes with PfAha1 for PfHsp90 in an MgCl2- and ATP-dependent manner, implying p23 helps set the composition of the chaperone cycle.

   Evidence GST pull-down competition assay between Pfp23 and PfAha1 for PfHsp90

   PMID:22100910

   Open questions at the time

   • Single method, single lab
   • Functional consequence of the competition for client maturation not tested
4. 2017 High

   Resolving the paralog question, biophysical and functional characterization showed P. falciparum encodes two highly divergent p23 proteins, both of which are elongated monomers with intrinsic chaperone and PfHsp90 ATPase-inhibiting activity, with PF3D7_0927000 (Pfp23A) being the more stable.

   Evidence Recombinant protein production, SAXS, thermal/chemical denaturation, aggregation suppression and ATPase inhibition assays

   PMID:29191421

   Open questions at the time

   • Distinct in vivo roles of Pfp23A versus Pfp23B not established
   • No structure of the p23-Hsp90 complex

• The cellular localization, parasite developmental role, client repertoire, and in vivo essentiality of PF3D7_0927000 remain unaddressed by the available corpus.
• No genetic knockout/knockdown phenotype reported
• No in-parasite localization or expression-timing data specific to PF3D7_0927000
• No identified Hsp90 client whose maturation depends on p23