Affinage · Plasmodium

PF3D7_1353900

proteasome subunit alpha type-7, putative

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1353900 (proteasome subunit alpha type-7, putative) is established in the available corpus only as a structural alpha-ring component of the P. falciparum 20S proteasome (Pf20S), whose intact architecture was resolved by cryo-EM to 3.6 Å (PMID:26863983). As part of the Pf20S alpha ring, it lies at the face engaged by the regulator PfPA28, which binds the alpha ring asymmetrically in cryo-EM structures of the Pf20S–PfPA28 complex, implicating the alpha ring in regulator docking (PMID:31384003). No catalytic activity, binding partner, post-translational modification, or individual functional role has been attributed specifically to PF3D7_1353900 beyond its membership in the 20S core in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2016 Low

    Before the Pf20S structure it was unclear how the parasite 20S core was organized; resolving the intact complex placed PF3D7_1353900 as one of the alpha-ring structural subunits.

    Evidence Cryo-EM single-particle analysis of the intact Pf20S complex at 3.6 Å

    PMID:26863983

    Open questions at the time
    • No function attributed specifically to PF3D7_1353900 beyond presence in the complex
    • No catalytic role assigned to this alpha subunit
    • No individual binding partners or PTMs identified
  2. 2019 Low

    How regulators engage the Pf20S alpha ring was unknown; structures of the Pf20S–PfPA28 complex showed asymmetric PfPA28 binding to the alpha ring, implicating alpha-ring subunits including alpha type-7 in regulator docking.

    Evidence Single-particle cryo-EM of Pf20S–PfPA28 at 3.8–3.9 Å, crystal structure of PfPA28, and molecular dynamics simulations

    PMID:31384003

    Open questions at the time
    • No contribution attributed specifically to PF3D7_1353900 within the alpha ring
    • Functional consequence of PfPA28 engagement for this subunit not defined
    • No direct interaction interface mapped for this individual subunit

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether PF3D7_1353900 has any subunit-specific role, catalytic contribution, regulatory function, or distinct binding partner beyond being an alpha-ring structural component remains uncharacterized in the available corpus.
  • No individual functional assignment to PF3D7_1353900
  • No genetic or biochemical perturbation of this specific subunit
  • No subunit-specific interactome or PTM data

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Complex memberships
P. falciparum 20S proteasome (Pf20S) core complexPf20S–PfPA28 complex

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 PF3D7_1353900 (proteasome subunit alpha type-7) is a structural component of the P. falciparum 20S proteasome (Pf20S) complex, whose overall architecture was resolved by cryo-EM to 3.6 Å; no specific mechanistic role was assigned to this alpha subunit beyond its presence in the complex. Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex Nature Low 26863983
2019 PF3D7_1353900 (proteasome alpha type-7 subunit) is part of the Pf20S alpha ring; cryo-EM structures of Pf20S capped with PfPA28 at 3.8–3.9 Å resolution show that PfPA28 binds the alpha ring asymmetrically, strongly engaging subunits on only one face of the 20S core, implicating the alpha ring (including alpha type-7) in regulator binding, but no specific function was assigned to this individual subunit. Single-particle cryo-EM of Pf20S–PfPA28 complex; crystal structure of PfPA28; molecular dynamics simulations Nature microbiology Low 31384003

Source papers

Stage 0 corpus · 7 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature 196 26863983
2012 The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention? International journal for parasitology. Drugs and drug resistance 64 24533266
2019 The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis. Nature microbiology 37 31384003
2021 Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome. Proceedings of the National Academy of Sciences of the United States of America 33 34548400
2023 Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors. Nature communications 21 38097652
2024 Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria. Cell chemical biology 11 39084225
2025 Optimization of Species-Selective Reversible Proteasome Inhibitors for the Treatment of Malaria. Journal of medicinal chemistry 1 41148577