SDHB

PF3D7_1212800 (SDHB) is the nuclear-encoded iron-sulfur subunit of Plasmodium falciparum complex II (succinate-ubiquinone oxidoreductase), predicted to contribute to mitochondrial succinate oxidation and expressed as a transcript in asexual erythrocytic stages (PMID:10779596). The 321-residue protein carries an N-terminal mitochondrial presequence for import and retains nearly all residues conserved for substrate binding and catalysis, while also containing a unicellular-organism-specific sequence deletion that distinguishes it from opisthokont orthologs (PMID:10779596). In gametocytes, SDHB comigrates with SDHA at ~530 kDa, placing it within a divergent, high-molecular-weight complex II assembly that incorporates novel putative subunits absent from opisthokonts (PMID:34155201). Beyond this assignment as a complex II iron-sulfur subunit and its assembly with SDHA, the precise catalytic contribution of SDHB and the identities of its novel assembly partners have not been characterized in the available corpus.

1. 2000 Medium

   Establishing whether P. falciparum possesses a canonical complex II iron-sulfur subunit answered whether the parasite encodes the machinery for mitochondrial succinate oxidation and how that subunit is targeted to the mitochondrion.

   Evidence Gene cloning, sequencing and alignment plus Northern blot of asexual blood-stage RNA

   PMID:10779596

   Open questions at the time

   • Catalytic activity and iron-sulfur cluster binding were inferred from conserved residues, not tested by mutagenesis or in vitro reconstitution
   • Mitochondrial import and presequence cleavage were predicted from sequence, not demonstrated experimentally
   • Functional consequence of the unicellular-organism-specific deletion is unknown
2. 2021 Medium

   Native complexome analysis addressed how SDHB assembles in vivo, revealing that it partners with SDHA in a divergent, larger-than-canonical complex II containing lineage-specific subunits.

   Evidence Complexome profiling (blue-native PAGE + quantitative mass spectrometry) across asexual blood stages and gametocytes

   PMID:34155201

   Open questions at the time

   • Comigration was not corroborated by reciprocal pulldown or structural analysis
   • The identities of the novel putative subunits in the ~530 kDa complex are not defined
   • Whether the same assembly forms in asexual stages, and its catalytic activity, are not established

• How SDHB contributes catalytically to succinate oxidation and what non-canonical proteins constitute its divergent complex II remain open.
• No direct enzymatic or iron-sulfur cluster assay for the P. falciparum protein
• Identities and functions of the novel complex II subunits are uncharacterized
• No genetic knockout/knockdown phenotype for SDHB in any life stage