SUFB

PF3D7_API04700 (SufB) is an apicoplast genome-encoded scaffold component of the SUF iron-sulfur cluster assembly pathway in Plasmodium falciparum (PMID:12594924, PMID:28695709). It physically interacts with the nuclear-encoded, plastid-imported ATPase PfSufC, an association demonstrated both by in vitro binding of an internal PfSufB region and by co-elution of endogenous PfSufB from parasite lysate with recombinant PfSufC (PMID:12594924, PMID:21722645). Together with PfSufD, PfSufB and PfSufC form a PfSufB–PfSufC2–PfSufD complex that functions as a scaffold capable of assembling [4Fe-4S] clusters in vitro, as shown by in vitro interaction assays, in vivo cross-linking, and reconstituted cluster assembly (PMID:28695709). Distinct from its bacterial homolog but resembling plant plastid SufB, recombinant apicoplast PfSufB itself exhibits ATPase activity, indicating a specialized function evolved in the plastid counterpart (PMID:21722645). Beyond its role as the scaffold subunit of this complex and its intrinsic ATPase activity, no further mechanistic detail for PF3D7_API04700 has been characterized in the available corpus.

1. 2003 Medium

   Establishing that the apicoplast genome-encoded SufB physically engages a nuclear-encoded partner was the first evidence that the apicoplast SUF machinery is assembled from proteins of two genomes.

   Evidence Physical interaction assay showing PfSufB (apicoplast-encoded) binds the imported ATPase PfSufC in P. falciparum

   PMID:12594924

   Open questions at the time

   • Method details limited; binding interface and stoichiometry not defined
   • No functional consequence of the interaction demonstrated
   • Involvement of additional subunits not addressed
2. 2011 High

   Confirming the PfSufB–PfSufC interaction with orthogonal methods and demonstrating intrinsic ATPase activity in PfSufB established that the apicoplast scaffold subunit has a specialized enzymatic property absent in bacterial SufB.

   Evidence In vitro pulldown with an internal PfSufB fragment, affinity co-elution of endogenous PfSufB from parasite lysate, and ATPase assay with recombinant protein in P. falciparum

   PMID:21722645

   Open questions at the time

   • Structural basis and residues of PfSufB ATPase activity not defined
   • Functional role of PfSufB ATPase within the assembly cycle unresolved
   • Whether SufD is part of the interaction not tested here
3. 2017 High

   Reconstituting a PfSufB–PfSufC2–PfSufD complex that assembles [4Fe-4S] clusters in vitro established PfSufB as the scaffold subunit on which apicoplast iron-sulfur clusters are built.

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

   PMID:28695709

   Open questions at the time

   • Mechanism of cluster transfer from the scaffold to downstream acceptors not defined
   • Role of PfSufB ATPase activity in the assembly reaction not established
   • In vivo essentiality and phenotype of PfSufB not tested

• How PfSufB's ATPase activity is coupled to cluster assembly and how the assembled [4Fe-4S] clusters are delivered to downstream apicoplast targets remain unknown.
• No structural model of the PfSufB–PfSufC2–PfSufD complex
• No downstream cluster acceptor identified
• Genetic requirement of PfSufB in parasite viability not established