RPL21

RPL21 (PF3D7_1426000) is a structural constituent protein of the 60S large subunit of the Plasmodium falciparum cytoplasmic 80S ribosome, as visualized in successive high-resolution cryo-EM structures of the parasite ribosome (PMID:24913268, PMID:26432834). It is present within the assembled 60S subunit that forms the functional target of translation-inhibiting antimalarials, including emetine and mefloquine, which act on the ribosome complex to block protein synthesis (PMID:24913268, PMID:28288098), and it is positioned within actively translating 80S ribosomes observed in the native cellular context of infected erythrocytes by in situ cryo-electron tomography (PMID:40825879). Beyond this membership in the ribosome complex, no experiment in the available corpus has specifically probed the function, interactions, or modifications of RPL21 itself; its role is defined entirely by its participation in the 60S subunit.

1. 2014 Medium

   Establishing whether PF3D7_1426000 is a component of the parasite ribosome answered where this protein resides functionally, placing it within the 60S large subunit of the 80S ribosome.

   Evidence Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å bound to emetine

   PMID:24913268

   Open questions at the time

   • No functional experiment isolates RPL21 or tests its specific contribution to translation
   • No RPL21-specific interactions or post-translational modifications characterized
2. 2015 Medium

   Independent cryo-EM reconstructions of blood-stage schizont ribosomes confirmed RPL21 as a reproducible structural member of the 60S subunit across atomic models built by flexible fitting.

   Evidence Sub-nanometer cryo-EM reconstructions with atomic model building in P. falciparum schizonts

   PMID:26432834

   Open questions at the time

   • Structural membership only; no assay of RPL21 function or assembly role
   • Single lab confirmation
3. 2017 Medium

   Structural determination of the ribosome with mefloquine bound clarified that the 60S-containing complex of which RPL21 is a part is the target through which the drug inhibits protein synthesis.

   Evidence Cryo-EM at 3.2 Å with mefloquine bound and mutagenesis of binding-site residues in P. falciparum

   PMID:28288098

   Open questions at the time

   • Mutagenesis targeted other ribosomal residues, not RPL21
   • RPL21's specific role in the drug interaction not addressed
4. 2025 Medium

   In situ cryo-electron tomography extended the picture from purified complexes to the native cellular context, placing RPL21 within actively translating ribosomes and revealing drug-induced shifts in ribosomal states and biogenesis.

   Evidence In situ cryo-ET of native P. falciparum-infected erythrocytes yielding eight high-resolution structures plus drug perturbation

   PMID:40825879

   Open questions at the time

   • No experiment specifically addresses RPL21 function within translating ribosomes
   • Cellular-context view does not resolve RPL21-specific dynamics or interactions

• Whether RPL21 has any function, interaction, or regulatory feature beyond passive membership in the 60S subunit remains uncharacterized.
• No RPL21-specific loss-of-function, knockdown, or biochemical assay exists in the corpus
• No RPL21 post-translational modifications or extra-ribosomal roles characterized
• No RPL21-specific binding partners identified beyond the ribosome complex