Affinage · Plasmodium

PF3D7_1328200

BRCA2 protein, putative

Audit flag: identity unverified
Annotated
2026-09-08
2 papers in source corpus 2 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1328200 (BRCA2) is a Plasmodium homologue of BRCA2 implicated in homologous recombination through its conserved BRC repeat motifs, which were computationally predicted to interact with RAD51 orthologues based on the human BRC4-RAD51 interaction fingerprint (PMID:12967658). In the rodent malaria parasite P. berghei, the BRC repeats of the ortholog directly bind Rad51 in a mammalian two-hybrid assay, confirming a physical BRCA2-Rad51 interaction in Plasmodium (PMID:35804459). Genetic knockout of P. berghei BRCA2 impairs parasite development across the life cycle — reducing parasitemia and shifting stage distribution, lowering gametocytemia and altering female gametocyte ratio, reducing oocyst numbers and ookinete development, and causing complete failure of sporogony — establishing that BRCA2 is required for normal blood-, gametocyte-, and mosquito-stage development and is especially critical for meiotic recombination during sporogony (PMID:35804459). Beyond the BRC-repeat/Rad51 interaction and the knockout phenotypes, no further biochemical or structural characterization of PF3D7_1328200 has been reported in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2003 Low

    Whether Plasmodium possesses a functional BRCA2-RAD51 homologous recombination pathway was unknown; sequence analysis addressed whether the parasite encodes a BRCA2 capable of RAD51 engagement.

    Evidence Comparative sequence analysis and computational fingerprint mapping against the human BRC4-RAD51 crystal structure

    PMID:12967658

    Open questions at the time
    • Purely computational inference — no direct experiment on the Plasmodium protein
    • Interaction with RAD51 predicted but not demonstrated
    • No functional role established
  2. 2022 Medium

    The predicted BRCA2-Rad51 interaction was tested directly, establishing that Plasmodium BRCA2 BRC repeats physically bind Rad51.

    Evidence Mammalian two-hybrid assay with P. berghei BRCA2 BRC repeats and PbRad51

    PMID:35804459

    Open questions at the time
    • Single method, single lab — no reciprocal or in-parasite interaction validation
    • Binding affinity and stoichiometry not quantified
    • Shown for the P. berghei ortholog, not PF3D7_1328200 itself
  3. 2022 Medium

    The functional requirement for BRCA2 across the parasite life cycle was unresolved; knockout defined its developmental roles and pinpointed sporogony as the most affected process.

    Evidence Genetic knockout with proliferation/differentiation assays in mice and mosquitoes plus transmission electron microscopy

    PMID:35804459

    Open questions at the time
    • Complementation/rescue not reported to confirm phenotype specificity
    • Whether sporogony failure reflects a direct meiotic HR defect at the molecular level not shown
    • Established in P. berghei; not directly demonstrated for PF3D7_1328200

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct biochemical role of PF3D7_1328200 in homologous recombination and its molecular contribution to meiotic recombination during sporogony remain uncharacterized.
  • No direct functional data on the P. falciparum protein PF3D7_1328200 itself
  • No structural model of the Plasmodium BRCA2-Rad51 complex
  • Mechanism by which BRCA2 loss blocks meiotic recombination not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
RAD51 / PBRAD51 (DIRECT INTERACTION VIA BRC REPEATS)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Computational sequence analysis identified partial BRCA2 homologues in two Plasmodium species containing BRC repeat motifs; using the crystal structure of the human BRC4-RAD51 complex to define interaction sequence fingerprints, it was predicted that the Plasmodium BRC repeats should be capable of interacting with RAD51 orthologues, suggesting conservation of the BRCA2-RAD51 homologous recombination pathway. Comparative sequence analysis and computational fingerprint mapping using the crystal structure of human BRC4-RAD51 complex DNA repair Low 12967658
2022 P. berghei BRCA2 (PbBrca2, the ortholog of PF3D7_1328200) BRC repeats interact with PbRad51 in a mammalian two-hybrid assay, establishing a direct physical interaction between BRCA2 and Rad51 in Plasmodium. Mammalian two-hybrid assay Parasites & vectors Medium 35804459
2022 Knockout of P. berghei BRCA2 (PbBrca2) caused reduced parasitemia with increased ring stage and decreased trophozoite stage counts, reduced gametocytemia, altered female gametocyte ratio, reduced oocyst number, impaired ookinete development, and complete failure of sporogony progression (as shown by transmission electron microscopy), demonstrating that BRCA2 is required for normal parasite development across multiple life cycle stages and especially for meiotic homologous recombination during sporogony. Genetic knockout (loss-of-function), parasite proliferation and differentiation assays in mice and mosquitoes, transmission electron microscopy Parasites & vectors Medium 35804459

Source papers

Stage 0 corpus · 2 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer. DNA repair 100 12967658
2022 Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes. Parasites & vectors 4 35804459