SKP1

SKP1 (PF3D7_1367000) is the adaptor subunit of a functional SCF (Skp1–Cullin-1–Fbox) ubiquitin E3 ligase complex in Plasmodium falciparum, where it physically associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein to form a complex with in vitro ubiquitination activity (PMID:38416790). Its stable partnership with PfFBXO1 has been independently confirmed by affinity purification–mass spectrometry (PMID:39915671). In the rodent malaria model P. berghei, the orthologous SKP1-containing SCF^FBXO1 complex is developmentally regulated and required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress from the host erythrocyte, and integrity of the apical and inner membrane complexes, with function coupled to calcium-dependent protein kinase 1 signalling (PMID:36898988). Beyond its role as the SCF adaptor subunit, no SKP1-specific molecular mechanism (e.g. substrate-recruitment determinants or a dedicated cellular phenotype attributable to SKP1 alone rather than the complex) has been characterized in the available corpus.

1. 2008 Low

   Before any experimental work, it was unknown whether apicomplexan parasites encode SCF ubiquitin ligase machinery; genome-wide domain analysis predicted a SKP1 orthologue in P. falciparum, framing it as a candidate E3 ligase component.

   Evidence HMM/Pfam domain profile search across apicomplexan genomes

   PMID:18545708

   Open questions at the time

   • Computational prediction only, with no biochemical or genetic validation of the P. falciparum protein
   • Complex membership, activity, and cellular role all left unaddressed
2. 2023 High

   To establish what the SKP1-containing complex actually does in vivo, the P. berghei ortholog was studied genetically, showing it assembles a conserved SCF^FBXO1 complex essential for nuclear segregation, centrosome partitioning, gamete egress, and IMC/apical complex integrity across development.

   Evidence Genetic tagging with reciprocal Co-IP, conditional knockouts with phenotypic analysis, ubiquitinomic substrate mapping, and epistasis with CDPK1 signalling in P. berghei

   PMID:36898988

   Open questions at the time

   • Phenotypes are ascribed to the SCF^FBXO1 complex, not to SKP1's own adaptor function in isolation
   • SKP1-specific substrate-recruitment contribution not separated from FBXO1
   • Findings are in P. berghei and not directly demonstrated for PF3D7_1367000
3. 2024 High

   It remained unproven that the predicted P. falciparum SKP1 forms a catalytically active E3 ligase; reconstitution and interaction assays confirmed PF3D7_1367000 associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein in a complex with in vitro ubiquitination activity.

   Evidence Immunoprecipitation, in vitro protein-protein interaction assay, and in vitro ubiquitination assay in P. falciparum

   PMID:38416790

   Open questions at the time

   • In vitro ubiquitination does not identify physiological substrates in P. falciparum
   • No structural basis for how SKP1 bridges Cullin-1 and the F-box protein is defined
   • Cellular phenotype of SKP1 loss in P. falciparum not tested
4. 2025 Medium

   An independent proteomic survey of PfFBXO1 interactors was needed to corroborate the SCF membership; it recovered PF3D7_1367000 as a stable PfFBXO1 partner, reinforcing SKP1's role as the SCF adaptor.

   Evidence Affinity purification–mass spectrometry of PfFBXO1 interactors in P. falciparum

   PMID:39915671

   Open questions at the time

   • Single Co-IP/MS pulldown without orthogonal validation of the specific SKP1 interaction
   • Does not add functional or substrate information for SKP1

• It remains unknown whether SKP1 (PF3D7_1367000) has any function or phenotype in P. falciparum distinct from its role as the SCF adaptor, and which physiological substrates the complex ubiquitinates through SKP1-mediated F-box recruitment.
• No conditional knockout of PF3D7_1367000 in P. falciparum reported
• No substrate attributable specifically to SKP1's adaptor activity
• No structural model of the P. falciparum SCF assembly