Affinage · Plasmodium

SufD

PF3D7_1103400 · iron-sulfur cluster assembly protein SufD

Annotated
2026-09-08
3 papers in source corpus 3 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SufD (PF3D7_1103400) is an apicoplast-localized component of the Plasmodium SUF iron-sulfur cluster biogenesis pathway required for asexual blood-stage survival (PMID:28695709, PMID:24586983, PMID:37166116). It assembles with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC into a PfSufB-C2-D scaffold complex that reconstitutes [4Fe-4S] clusters in vitro, and within this complex SufD enhances the ATPase activity of PfSufC (PMID:28695709). SufD is refractory to gene deletion in P. berghei blood stages and lethal upon conditional deletion in P. falciparum (PMID:24586983, PMID:37166116); unlike deletion of the cysteine desulfurase SufS, loss of SufD leaves the apicoplast organelle and its genome intact, establishing that its essential function lies specifically in Fe-S cluster assembly rather than organelle maintenance (PMID:37166116). Beyond its role in this scaffold complex and Fe-S cluster biogenesis, no further mechanistic detail about SufD has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2014 High

    Establishing whether SufD is dispensable and where it acts localized the protein to the apicoplast and demonstrated it is required for blood-stage growth, setting up its candidacy as an essential metabolic factor.

    Evidence Targeted gene deletion attempt and endogenous fluorescent tagging with microscopy in P. berghei

    PMID:24586983

    Open questions at the time
    • Deletion refractoriness alone does not distinguish essentiality from a technical failure to recover deletants
    • Does not identify SufD's molecular activity or binding partners
    • Localization shown in P. berghei only
  2. 2017 High

    Reconstituting the SufB-C2-D complex answered how SufD contributes biochemically, showing it is a scaffold subunit for [4Fe-4S] assembly and a positive regulator of PfSufC ATPase activity.

    Evidence In vitro interaction and in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, and ATPase activity assay in P. falciparum

    PMID:28695709

    Open questions at the time
    • Stoichiometry and structural basis of the SufB-C2-D scaffold not resolved
    • Mechanism by which SufD enhances PfSufC ATPase activity not defined
    • Downstream Fe-S recipient apoproteins not identified
  3. 2023 High

    Conditional deletion resolved whether SufD's essentiality reflects Fe-S biogenesis or organelle upkeep, showing loss is lethal without disrupting the apicoplast or its genome and thereby assigning its essential role specifically to cluster assembly.

    Evidence Conditional gene deletion by chemical bypass with apicoplast organelle integrity and organellar genome retention readouts in P. falciparum

    PMID:37166116

    Open questions at the time
    • The essential Fe-S-dependent client pathway that makes SufD indispensable is not pinpointed
    • Does not establish in vivo the scaffold mechanism inferred from in vitro reconstitution

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological Fe-S cluster recipient apoproteins that depend on SufD and the structural mechanism of the SufB-C2-D scaffold remain unknown.
  • No identified downstream Fe-S client accounting for essentiality
  • No structural model of the SufB-C2-D complex
  • Mechanism of SufC ATPase stimulation by SufD undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
PFSUFBPFSUFC
Complex memberships
PfSufB-C2-D scaffold complex

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 PfSufD (PF3D7_1103400) forms a complex with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC, as demonstrated by in vitro interaction experiments and in vivo cross-linking. The PfSufB-C2-D complex functions as a scaffold to assemble [4Fe-4S] clusters in vitro, and PfSufD enhances PfSufC ATPase activity. In vitro interaction experiments, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, ATPase activity assay The FEBS journal High 28695709
2014 SufD (PF3D7_1103400) is refractory to targeted gene deletion in Plasmodium berghei blood stages, indicating it is essential for asexual blood stage growth in vivo. Endogenous tagging with a fluorescent marker demonstrated that SufD localizes to the apicoplast. Targeted gene deletion attempt (P. berghei), fluorescent tagging of endogenous locus, fluorescence microscopy PloS one High 24586983
2023 SufD (PF3D7_1103400) is essential for Plasmodium falciparum parasite survival; deletion using a chemical bypass method was lethal. Unlike deletion of the cysteine desulfurase SufS, deletion of SufD did not disrupt the apicoplast organelle or cause loss of the organellar genome, indicating SufD's essential role is specifically in iron-sulfur cluster assembly rather than organelle maintenance. Conditional gene deletion using chemical bypass, apicoplast organelle integrity assay, organellar genome retention assay eLife High 37166116

Source papers

Stage 0 corpus · 3 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 [Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite. The FEBS journal 30 28695709
2014 Identification of vital and dispensable sulfur utilization factors in the Plasmodium apicoplast. PloS one 27 24586983
2023 The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification. eLife 13 37166116