AHA1

PF3D7_0306200 (AHA1) is a co-chaperone of the Plasmodium falciparum Hsp90 chaperone cycle that physically interacts with PfHsp90 and stimulates its ATPase activity, consistent with a role in promoting client protein activation (PMID:22100910). The interaction is ATP- and MgCl2-dependent and is disrupted by high salt, indicating a polar binding mode, and it is competed by the co-chaperone Pfp23; site-directed mutagenesis identified the polar residue N108 of PfAha1 as essential for PfHsp90 binding (PMID:22100910). Beyond this characterization of PfHsp90 binding and ATPase stimulation (PMID:22100910), no further mechanistic detail—including client proteins, in vivo phenotype, or structural model—has been characterized in the available corpus.

1. 2011 Medium

   Whether P. falciparum encodes a functional Aha1 co-chaperone capable of engaging and activating PfHsp90 was unknown; this work established a direct, nucleotide-dependent interaction and demonstrated that PfAha1 stimulates PfHsp90 ATPase activity, defining its role in the parasite chaperone cycle.

   Evidence In vivo split-ubiquitin assay and in vitro GST pull-down under defined ATP/MgCl2/salt conditions, N108 site-directed mutagenesis, and ATPase activity assay

   PMID:22100910

   Open questions at the time

   • Findings derive from a single lab without independent replication
   • No client proteins of the PfHsp90–PfAha1 module identified
   • No in vivo parasite phenotype or essentiality data for PF3D7_0306200

• How PfAha1 activity is integrated with other co-chaperones during client maturation, and whether it is required for parasite viability or drug response, remains unresolved.
• No structural model of the PfHsp90–PfAha1 complex
• Functional interplay with Pfp23 beyond competition for binding is uncharacterized
• No genetic knockout/knockdown data in the parasite