PDI-11

PF3D7_1134100 (PDI-11) is one of nine protein disulfide isomerase-like molecules encoded by Plasmodium falciparum, assigned to the PfPDI family by chromosomal location, sequence, phylogeny, and thioredoxin-domain composition (PMID:16806221). Direct biochemical characterization specific to PDI-11 is limited: in a Pichia pastoris heterologous system, overproduction of a P. falciparum PDI increased the fraction of the correctly folded Pfs25(A) isoform and altered its O-linked glycosylation, indicating that a PfPDI can influence disulfide-dependent folding and post-translational modification of a heterologous substrate (PMID:16274825), but this study did not unambiguously resolve whether the enzyme assayed was PDI-11 or another family member. Beyond family membership (PMID:16806221) and this yeast folding activity attributed to a PfPDI (PMID:16274825), no PDI-11-specific substrate, catalytic mechanism, native localization, or in-parasite function has been experimentally established in the available corpus.

1. 2003 Low

   Whether a P. falciparum PDI physically engages the heme byproduct of hemoglobin digestion was addressed to place thiol-oxidoreductases in the parasite's heme-handling environment, but the recovered PDI was not resolved to the gene level.

   Evidence Ferriprotoporphyrin IX (FP)-agarose affinity pulldown from parasite lysate with mass spectrometry identification

   PMID:12748176

   Open questions at the time

   • The specific PDI family member recovered was not identified at the gene level, so attribution to PDI-11 cannot be confirmed
   • No functional consequence of FP binding was established
   • Single pulldown without reciprocal or genetic validation
2. 2005 Low

   The question of whether a PfPDI possesses functional disulfide-folding activity was tested by asking if it could improve folding of a disulfide-rich malaria antigen in a heterologous host.

   Evidence Heterologous overexpression of PfPDI in Pichia pastoris co-expressing Pfs25, with mass spectrometry and isoform-ratio analysis of the folded product

   PMID:16274825

   Open questions at the time

   • The identity of the assayed 'PfPDI' as PF3D7_1134100 versus another family member is not unambiguously established
   • Activity was measured in yeast, not in Plasmodium
   • No native substrate or in-parasite folding role was demonstrated
3. 2006 Low

   To define the enzyme's identity, PDI-11 was formally delineated as a distinct member of the P. falciparum PDI family, establishing its sequence, thioredoxin-domain architecture, and phylogenetic placement.

   Evidence Gene isolation, sequence and phylogenetic analysis, and thioredoxin-domain characterization of nine PfPDI-like molecules

   PMID:16806221

   Open questions at the time

   • Bioinformatic/sequence characterization only; no direct biochemical assay was performed on PDI-11 itself
   • Native localization within the parasite was not determined
   • Catalytic activity and substrates specific to PDI-11 remain unassigned
4. 2022 Low

   A means to capture the endogenous substrates of Trx-domain oxidoreductases, including PDI family members, was developed to move beyond bioinformatic assignment toward direct substrate mapping.

   Evidence Cell-permeable divinyl sulfone (DVSF) activity-based crosslinking trapping mixed-disulfide intermediates, followed by immunoprecipitation-mass spectrometry (methodological/protocol paper)

   PMID:35340291

   Open questions at the time

   • Methodological paper; no PDI-11-specific substrate is reported
   • Applicability is stated for PDI family members generally, not demonstrated for PDI-11
   • No validation of trapped complexes for this gene

• It remains unknown whether PDI-11 catalyzes disulfide isomerization on defined native Plasmodium substrates, where it localizes in the parasite, and what its role is in the parasite life cycle, as no experiment in the corpus assigns a biochemical activity or substrate unambiguously to PF3D7_1134100.
• No native substrate identified specifically for PDI-11
• No in-parasite localization or genetic essentiality data
• The activity attributed to 'PfPDI' in yeast has not been genetically tied to PF3D7_1134100