Affinage · Plasmodium

NSF

PF3D7_0303000 · N-ethylmaleimide-sensitive fusion protein

Annotated
2026-09-08
11 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P. falciparum NSF (PF3D7_0303000) is an 89-kDa membrane-associated protein implicated in vesicular trafficking and protein export during blood-stage parasite development (PMID:11278971). Subcellular fractionation places it predominantly in the particulate fraction, and imaging localizes it both within the parasite—associated with organelles including food vacuoles—and in vesicular structures exported to the host erythrocyte cytoplasm (PMID:11278971). This export begins at the early trophozoite stage, ceases by the merozoite stage, and is blocked by brefeldin A, situating NSF within the brefeldin A-sensitive secretory pathway (PMID:11278971). Beyond this localization and pathway assignment, the mechanistic activity of PF3D7_0303000—including any ATPase function, membrane-fusion role, or interacting partners—has not been characterized in the available corpus; a single mass-spectrometry pulldown raises the possibility that it is a sumoylation target, but this remains uncharacterized (PMID:18547337).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2001 Medium

    Establishing whether P. falciparum encodes an NSF-like protein and where it acts addressed how the parasite might drive vesicular trafficking, revealing a membrane-associated protein that is exported into the host erythrocyte via a brefeldin A-sensitive route.

    Evidence Subcellular fractionation, immunoblotting, immunofluorescence, immunoelectron microscopy, and brefeldin A inhibition in blood-stage P. falciparum

    PMID:11278971

    Open questions at the time
    • No direct demonstration of ATPase or membrane-fusion activity for PF3D7_0303000
    • No interacting partners or SNARE substrates identified
    • No genetic or reconstitution evidence linking NSF to a specific export cargo
  2. 2008 Low

    A proteomic survey of sumoylation targets asked whether NSF is post-translationally modified, tentatively placing it among candidate sumoylated proteins consistent with its vesicular localization.

    Evidence Two-step anti-FLAG/anti-PfSUMO immunoprecipitation followed by LC-MS/MS in blood-stage parasites

    PMID:18547337

    Open questions at the time
    • Single pulldown/MS identification with no direct validation that NSF itself is sumoylated
    • No mapped sumoylation site or functional consequence established
    • Not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether PF3D7_0303000 possesses catalytic (ATPase) activity, engages defined SNARE or trafficking partners, and how its erythrocyte export is regulated remains unresolved.
  • No biochemical demonstration of enzymatic activity
  • No validated interactome or complex membership
  • No loss-of-function phenotype defining its role in export

Mechanism profile

Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 P. falciparum NSF (PfNSF/PF3D7_0303000) is an 89-kDa protein that is approximately 90% associated with the particulate (membrane-bound) fraction after parasite homogenization, indicating membrane-bound nature. It is present both within the parasite cell (associated with organelles such as food vacuoles) and exported to vesicular structures in the erythrocyte cytoplasm. Export occurs at the early trophozoite stage and terminates at the merozoite stage, and is inhibited by brefeldin A (IC50 ~9 µM), placing it in the brefeldin A-sensitive secretory pathway. Subcellular fractionation, immunoblotting with polyclonal antibodies against conserved NSF region, immunofluorescence, immunoelectron microscopy, brefeldin A inhibition assay, Northern blotting, RT-PCR The Journal of biological chemistry Medium 11278971
2008 NSF (PF3D7_0303000) was identified by LC-MS/MS in a two-step immunoprecipitation (anti-FLAG/anti-PfSUMO) designed to capture sumoylated proteins in P. falciparum blood-stage parasites, suggesting NSF may be a target of sumoylation; the authors note this is consistent with its known cytoplasmic vesicular localization. Two-step immunoprecipitation followed by LC-MS/MS mass spectrometry Cellular microbiology Low 18547337

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 A homologue of N-ethylmaleimide-sensitive factor in the malaria parasite Plasmodium falciparum is exported and localized in vesicular structures in the cytoplasm of infected erythrocytes in the brefeldin A-sensitive pathway. The Journal of biological chemistry 62 11278971
2026 Mechanisms and Therapeutic Potential of Nutritional Immunity. Pathogens (Basel, Switzerland) 0 41754428
2025 Role of novel mutations in food vacuole transporters beyond K13-mediated artemisinin resistance in Plasmodium falciparum. Antimicrobial agents and chemotherapy 0 41025646
2021 A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum. PLoS pathogens 0 34780541
2019 A genome-wide analysis of coatomer protein (COP) subunits of apicomplexan parasites and their evolutionary relationships. BMC genomics 0 30704415
2018 ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites. mBio 0 29295911
2018 The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. PLoS biology 0 29529020
2016 Plasmodium falciparum Rab1A Localizes to Rhoptries in Schizonts. PloS one 0 27348424
2016 Host cell remodeling by pathogens: the exomembrane system in Plasmodium-infected erythrocytes. FEMS microbiology reviews 0 27587718
2009 A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation. Malaria journal 0 19374766
2008 Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments. Cellular microbiology 0 18547337