VPS11

PF3D7_0502000 (VPS11) is a conserved subunit of the Vps-C core tethering machinery in Plasmodium falciparum (PMID:40626728, PMID:24086721). Co-immunoprecipitation of PfVps16 followed by mass spectrometry established that VPS11 co-purifies with the canonical Vps-C members Vps16, Vps18, and Vps33, together with the CORVET-specific component Vps3, placing VPS11 within this membrane-tethering complex (PMID:40626728). Comparative genomic analysis across apicomplexan genomes shows VPS11 is one of the well-conserved Vps-C core subunits shared by the HOPS and CORVET complexes, in contrast to other multisubunit tethering components lost in Apicomplexa (PMID:24086721). VPS11 is also susceptible to oxidative post-translational modification, forming 4-HNE adducts at defined sites under plakortin-induced oxidative stress (PMID:26459031). Beyond its assignment to the Vps-C complex by interaction and sequence conservation, no direct functional experiments on VPS11 itself — such as knockdown, knockout, or activity assays — have been reported in the available corpus.

1. 2013 Low

   Before experimental interrogation, it was unknown whether the Vps-C tethering machinery is conserved in Apicomplexa; bioinformatic analysis established that VPS11 is a retained core subunit, marking it as a candidate component of Plasmodium endolysosomal trafficking.

   Evidence Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes

   PMID:24086721

   Open questions at the time

   • Computational prediction only, with no experimental validation of VPS11 expression, interactions, or function
   • Does not establish which complex (HOPS vs CORVET) VPS11 participates in physiologically
   • No subcellular localization for VPS11
2. 2015 Low

   It was unknown whether VPS11 is a target of antimalarial-induced oxidative stress; identification of site-specific 4-HNE adducts showed the protein is chemically modified under pro-oxidant drug treatment.

   Evidence Mass spectrometry identification of 4-HNE protein conjugates in plakortin-treated parasites

   PMID:26459031

   Open questions at the time

   • No functional consequence of the modification on VPS11 activity or complex assembly demonstrated
   • Does not establish whether oxidative modification of VPS11 contributes to the drug's mechanism of action
   • Single MS identification without independent confirmation
3. 2025 Medium

   The predicted membership of VPS11 in the Vps-C core needed experimental confirmation; Co-IP/MS with PfVps16 as bait showed VPS11 co-purifies with all canonical Vps-C members and the CORVET component Vps3, confirming its incorporation into the tethering complex.

   Evidence Immunoprecipitation of PfVps16 followed by mass spectrometry

   PMID:40626728

   Open questions at the time

   • Bait was Vps16, not VPS11 itself, so no VPS11-directed reciprocal validation was performed
   • Single lab, single study
   • Does not distinguish VPS11's specific contribution to HOPS versus CORVET function

• No direct functional experiment on VPS11 itself has been performed; its cellular role, essentiality, tethering activity, and contribution to specific trafficking pathways in P. falciparum remain uncharacterized.
• No VPS11 knockout, knockdown, or conditional-depletion phenotype reported
• No VPS11-directed localization or structural data
• Role of VPS11 in endolysosomal or apical-organelle biogenesis untested experimentally