PF3D7_1142600

PF3D7_1142600 (L35ae) is a structural constituent of the large (60S) subunit of the Plasmodium falciparum 80S ribosome, established through successive high-resolution cryo-EM structures of the assembled Pf80S ribosome (PMID:24913268, PMID:28288098) and cryo-EM reconstructions of ribosomes purified from blood-stage schizonts (PMID:26432834). Its incorporation into actively translating ribosomes within infected human erythrocytes has been directly visualized by in situ cryo-electron tomography (PMID:40825879). Beyond this membership in the assembled 60S subunit, no enzymatic activity, individual binding partner, post-translational modification, or discrete functional role has been experimentally characterized for L35ae in the available corpus; every finding places it as one component of the ribosomal complex rather than assigning it a distinct mechanism.

1. 2014 Medium

   Establishing that L35ae is a bona fide component of the P. falciparum ribosome required a high-resolution structure of the assembled particle; the first such structure placed L35ae within the 60S large subunit.

   Evidence 3.2 Å cryo-EM structure of the emetine-bound Pf80S ribosome

   PMID:24913268

   Open questions at the time

   • No functional role for L35ae beyond presence in the complex
   • No binding partner or interface specific to L35ae defined
   • Structure from a single drug-bound state
2. 2015 Medium

   Whether L35ae is present in ribosomes from a physiologically relevant blood stage was addressed by reconstructing ribosomes purified from schizont-stage parasites, confirming its membership in the large subunit under native purification.

   Evidence Five sub-nanometer cryo-EM reconstructions with atomic models built by flexible fitting from schizont-stage ribosomes

   PMID:26432834

   Open questions at the time

   • No mechanistic role assigned to L35ae
   • No stage-specific expression or regulation of L35ae shown
   • Contribution of L35ae to ribosome function not tested
3. 2017 Medium

   A further high-resolution structure of a drug-bound Pf80S ribosome reconfirmed L35ae as a stable structural element of the large subunit across different ligand-bound states.

   Evidence 3.2 Å cryo-EM structure of Pf80S bound to (+)-mefloquine (mutagenesis targeted other ribosomal proteins, not L35ae)

   PMID:28288098

   Open questions at the time

   • L35ae itself was not mutated or functionally probed
   • No interaction with the drug or catalytic centers demonstrated for L35ae
4. 2025 Medium

   Whether L35ae is incorporated into ribosomes engaged in translation in the native cellular environment was resolved by in situ imaging, confirming its presence in actively translating 80S ribosomes inside infected erythrocytes.

   Evidence Eight high-resolution in situ cryo-electron tomography structures of P. falciparum-infected human erythrocytes

   PMID:40825879

   Open questions at the time

   • No distinct functional contribution of L35ae to translation demonstrated
   • No dynamics or conformational role specific to L35ae resolved

• It remains unknown whether L35ae has any function beyond serving as a structural component of the 60S subunit, including any binding partner, post-translational modification, or role in ribosome assembly or translational regulation specific to this protein.
• No genetic knockout or knockdown of L35ae reported
• No L35ae-specific interaction or modification characterized
• No essentiality or phenotype tied to L35ae itself