RPL5

PF3D7_1424100 (RPL5) is a component of the large (60S) subunit of the P. falciparum 80S cytoplasmic ribosome, whose structure has been resolved by cryo-EM to 3.2 Å (PMID:24913268) and further characterized across multiple translational states, including in situ within infected erythrocytes during the elongation cycle (PMID:40825879). Structural comparison of the parasite 60S subunit with mammalian ribosomes has identified features that distinguish the malarial ribosome (PMID:26432834), and the ribosome has been validated as the target of antimalarial drugs including emetine at the small-subunit E-site (PMID:24913268) and mefloquine at the GTPase-associated centre (PMID:28288098). Beyond its membership in the 60S subunit as defined by these structural studies, no mechanistic function, interaction, or active-site contribution specific to RPL5 has been characterized in the available corpus.

1. 2014 Medium

   Establishing the atomic architecture of the P. falciparum ribosome was needed to place RPL5 in a defined structural context; the first high-resolution cryo-EM structure situated RPL5 as a 60S subunit component of the intact 80S ribosome.

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

   PMID:24913268

   Open questions at the time

   • No RPL5-specific function, interaction, or active-site role resolved beyond subunit membership
   • Emetine binds the small subunit, not RPL5
2. 2015 Medium

   To determine whether the parasite ribosome differs from the host, multiple cryo-EM reconstructions were built into atomic models, identifying 60S features that distinguish the malarial ribosome from mammalian ribosomes.

   Evidence Five cryo-EM reconstructions of 80S ribosomes from blood-stage schizonts with atomic model building by flexible fitting

   PMID:26432834

   Open questions at the time

   • Distinguishing features not attributed specifically to RPL5
   • No functional consequence assigned to RPL5
3. 2017 Medium

   To validate the ribosome as an antimalarial drug target, the structure was solved with mefloquine bound and binding-site residues mutated, confirming drug action at the GTPase-associated centre of the 60S-containing ribosome.

   Evidence Cryo-EM at 3.2 Å with mefloquine bound plus site-directed mutagenesis of binding-site residues

   PMID:28288098

   Open questions at the time

   • Mefloquine-binding site not attributed to RPL5
   • No RPL5 involvement in drug binding demonstrated
4. 2025 Medium

   To capture the ribosome under physiological conditions, in situ cryo-ET resolved actively translating states inside infected erythrocytes, placing the RPL5-containing 60S subunit within the native elongation cycle.

   Evidence In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution translating-state structures

   PMID:40825879

   Open questions at the time

   • No dynamic or functional role assigned to RPL5 within the elongation cycle
   • RPL5 characterized only as a structural constituent

• Whether RPL5 has any function, interaction, or active-site contribution distinct from its structural role in the 60S subunit remains uncharacterized.
• No RPL5-specific knockdown, mutagenesis, or interaction study
• No assembly or rRNA-binding role established for RPL5
• No functional distinction from bulk 60S subunit