RPL39

RPL39 (PF3D7_0611700) is a structural component of the 60S large subunit of the Plasmodium falciparum 80S cytoplasmic ribosome, resolved as part of the assembled particle across multiple high-resolution cryo-EM structures (PMID:24913268, PMID:28288098) and, most recently, within the native translating ribosome imaged in situ by cryo-electron tomography inside infected erythrocytes (PMID:40825879). Its presence in the 60S subunit is consistent across ribosomes purified from blood-stage schizonts and within actively translating states in the cellular context (PMID:26432834, PMID:40825879). Beyond its membership in the 60S large subunit of the malarial ribosome, no specific functional, enzymatic, or regulatory role has been assigned to RPL39 (PF3D7_0611700) in the available corpus; the structural studies that resolve it are directed at the ribosome as a whole and as a drug target rather than at this protein individually (PMID:24913268, PMID:28288098, PMID:40825879).

1. 2014 Medium

   The first atomic-resolution view of the malarial ribosome was needed to define its protein composition; this established RPL39 as a resolved constituent of the 60S large subunit.

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

   PMID:24913268

   Open questions at the time

   • No functional experiment targets RPL39 individually
   • No role beyond structural membership in the 60S subunit is defined
2. 2015 Medium

   Whether the ribosome composition held in physiologically relevant blood-stage parasites was open; sub-nanometer reconstructions from schizont ribosomes confirmed RPL39 as a 60S component in native blood-stage ribosomes.

   Evidence Cryo-EM reconstruction with flexible fitting of atomic models from blood-stage schizont ribosomes

   PMID:26432834

   Open questions at the time

   • No individual functional assay on RPL39
   • Interactions or assembly role of RPL39 within the 60S not addressed
3. 2017 Medium

   Structural characterization in the context of antimalarial drug binding tested whether the ribosome is the drug target; RPL39 was again resolved as part of the 60S subunit, with mutagenesis confirming the ribosome as the target.

   Evidence Cryo-EM at 3.2 Å with mefloquine bound, plus site-directed mutagenesis and parasite resistance assay

   PMID:28288098

   Open questions at the time

   • Drug-target validation concerns the ribosome, not RPL39 specifically
   • No evidence RPL39 contributes to drug binding or resistance
4. 2025 Medium

   Whether the composition observed in purified ribosomes reflects the native translating ribosome in cells was unresolved; in situ cryo-ET placed RPL39 within the 60S subunit of actively translating ribosomes inside infected erythrocytes.

   Evidence In situ cryo-electron tomography of native translating ribosomes within P. falciparum-infected erythrocytes

   PMID:40825879

   Open questions at the time

   • Elongation-state and biogenesis changes were observed for the ribosome, not attributed to RPL39
   • No functional dependency of translation on RPL39 established

• Whether RPL39 has any function beyond serving as a 60S structural subunit — in ribosome assembly, translation fidelity, or drug interaction — remains uncharacterized in the available corpus.
• No genetic or biochemical perturbation of RPL39 reported
• No specific molecular activity assigned to RPL39
• No interaction partners specific to RPL39 defined beyond the ribosome