PF3D7_1026800

PF3D7_1026800 (S2) is a component of the 40S small subunit of the P. falciparum 80S cytoplasmic ribosome, resolved as one of many small-subunit proteins in high-resolution cryo-EM structures of the intact ribosome (PMID:24913268, PMID:28288098). These structures were determined in complex with translation-inhibiting antimalarials—emetine bound at the small-subunit E-site to block mRNA/tRNA translocation (PMID:24913268) and (+)-mefloquine bound at the GTPase-associated centre (PMID:28288098)—and the native ribosome containing S2 has been captured in actively translating elongation states by in situ cryo-electron tomography inside infected erythrocytes (PMID:40825879). Proteomic co-melting profiling confirms S2 as a constitutive member of the ribosome complex across the intraerythrocytic developmental cycle (PMID:41315737). Beyond its membership in the 40S subunit within the translating ribosome, no mechanistic function has been attributed to S2 individually in the available corpus; all findings characterize the ribosome as a whole rather than S2 in isolation.

1. 2014 Medium

   Establishing whether S2 could be placed structurally required an atomic model of the P. falciparum ribosome; the first cryo-EM structure resolved the 80S ribosome including the 40S subunit that contains S2, and localized emetine at the small-subunit E-site where it blocks translocation.

   Evidence Cryo-EM structure determination of the 80S ribosome at 3.2 Å in complex with emetine

   PMID:24913268

   Open questions at the time

   • S2 is visualized only as one of many small-subunit proteins; no S2-specific function or interaction is tested
   • does not establish any role for S2 distinct from the assembled subunit
2. 2017 Medium

   To define a second antimalarial's ribosomal target, the 80S structure containing S2 was solved with (+)-mefloquine bound to the GTPase-associated centre, confirming inhibition of protein synthesis at the ribosome.

   Evidence Cryo-EM at 3.2 Å with mutagenesis of the binding residues

   PMID:28288098

   Open questions at the time

   • The drug binding site is not on or attributed to S2
   • S2 remains uncharacterized as an individual protein
3. 2023 Low

   The question of whether ribosome composition is uniform across the parasite life cycle was addressed by profiling 40S subunit heterogeneity, raising the possibility of stage-specific ribosome variants that include the S2-containing small subunit.

   Evidence Ribosome fractionation and structural/proteomic analysis across life-cycle stages

   PMID:37053161

   Open questions at the time

   • Methods are not described in detail in the abstract
   • S2 is inferred as a small-subunit member but not individually shown to vary
   • no functional consequence of any compositional change is demonstrated
4. 2025 Medium

   To move from purified structures to the native context, in situ cryo-ET resolved the S2-containing ribosome in multiple actively translating states inside infected erythrocytes, capturing elongation-cycle intermediates and drug-induced changes in ribosome localization.

   Evidence In situ cryo-electron tomography in P. falciparum-infected erythrocytes yielding eight ribosome structures

   PMID:40825879

   Open questions at the time

   • S2 is one of many resolved proteins with no individual functional assignment
   • no perturbation of S2 specifically is performed
5. 2025 Low

   Whether S2 is a stable versus dynamic ribosome component was probed by complexome-wide thermal proteome profiling, which detected S2 co-melting with the ribosome across the intraerythrocytic cycle, consistent with constitutive 40S membership.

   Evidence Meltome-assisted profiling of protein complexes (MAP-X) across seven IDC timepoints in intact cells

   PMID:41315737

   Open questions at the time

   • Membership is inferred from co-melting, not from a direct functional assay on S2
   • no S2-specific interaction, modification, or activity is measured

• No experiment in the available corpus has assigned any function, interaction, or phenotype to S2/PF3D7_1026800 as an individual protein distinct from its structural membership in the 40S subunit; whether S2 has any specialized role remains unaddressed.
• No S2-specific knockdown, knockout, or complementation
• no S2-specific binding partner or post-translational regulation identified
• no evidence that S2 contributes to any stage-specific ribosome specialization