RPT1

RPT1 (PF3D7_1311500) is one of six AAA+ ATPases of the 19S regulatory particle of the P. falciparum 26S proteasome (PMID:30323024). Beyond its membership in the regulatory particle, RPT1 links proteasome regulation to cGMP signaling: it directly binds the cGMP-dependent protein kinase PfPKG in vitro through a fragment bearing a PfPKG consensus phosphorylation site, and a peptide spanning that site both competes for PfPKG binding and is efficiently phosphorylated by PfPKG, establishing RPT1 as a direct PfPKG substrate (PMID:30323024). In P. berghei, an IP/MS interactome anchored on the Rpt3 ortholog co-enriched all six Rpt ATPases including the RPT1 ortholog but recovered no 20S core subunits, consistent with RPT1 being a stable component of the 19S ATPase ring whose association with the 20S core is transient (PMID:41373862). No functional or structural characterization of RPT1's ATPase activity or its role in substrate unfolding within the parasite has been reported in the available corpus.

1. 2018 Medium

   Established that RPT1 physically and enzymatically connects the proteasome regulatory particle to cGMP signaling, answering whether PfPKG has a direct proteasomal substrate.

   Evidence Yeast two-hybrid screen, in vitro binding, peptide competition, and in vitro kinase assays in P. falciparum

   PMID:30323024

   Open questions at the time

   • Phosphorylation shown on a peptide, not on full-length RPT1 in parasites
   • Functional consequence of RPT1 phosphorylation on proteasome activity unknown
   • In vivo relevance of the RPT1-PfPKG interaction not demonstrated
2. 2025 Low

   Confirmed RPT1 as an integral member of the six-subunit Rpt ATPase ring of the 19S regulatory particle and indicated a dynamic 19S-20S association in the parasite.

   Evidence IP/MS interactome of PbRpt3-mCherry in P. berghei trophozoite-schizont extracts

   PMID:41373862

   Open questions at the time

   • Single Co-IP/MS experiment with no functional follow-up specific to RPT1
   • Shown for the P. berghei ortholog, not P. falciparum RPT1 directly
   • Absence of 20S subunits is interpretive; not tested by orthogonal assay

• Whether PfPKG phosphorylation of RPT1 alters proteasome assembly, ATPase activity, or substrate degradation during the parasite life cycle remains unresolved.
• No functional link between RPT1 phosphorylation and proteolytic output
• No structural model of RPT1 within the parasite 19S particle
• No genetic assessment of RPT1 essentiality or phenotype