PF3D7_0821700

PF3D7_0821700 (L22) is a nuclear genome-encoded large-subunit ribosomal protein that serves as a structural component of the 60S large subunit of the P. falciparum cytoplasmic 80S ribosome (PMID:24913268). It has been resolved within the large subunit in successive high-resolution cryo-EM structures of the parasite ribosome purified from blood-stage schizonts (PMID:24913268, PMID:26432834) and visualized in situ in actively translating native ribosomes inside infected human erythrocytes by cryo-electron tomography (PMID:40825879). Molecular modeling predicts that L22 contributes together with the apicoplast-encoded PfRpl4 to the polypeptide exit tunnel that can be occupied by azithromycin, and in vitro azithromycin-resistance selection left the L22 sequence unchanged while mutations arose in PfRpl4, indicating a structural exit-tunnel role for L22 rather than a direct drug-resistance determinant (PMID:17110371). Beyond its membership in the ribosomal large subunit and its predicted exit-tunnel contribution, no direct biochemical or mutagenesis experiments defining a unique function for L22 have been characterized in the available corpus.

1. 2006 Low

   To locate the target of azithromycin action in the parasite, resistance selection tested whether L22, predicted to line the polypeptide exit tunnel, was itself a resistance determinant, establishing L22's inferred structural role in the tunnel while excluding it as a mutational drug-resistance site.

   Evidence In vitro azithromycin resistance selection with sequencing of resistant lines and molecular modeling of the exit tunnel in P. falciparum 7G8 and Dd2

   PMID:17110371

   Open questions at the time

   • Structural role inferred from modeling and absence of mutations, not from direct biochemical assay of L22
   • No mutagenesis of L22 to test its exit-tunnel contribution
   • Interaction with PfRpl4 predicted, not experimentally demonstrated
2. 2014 Medium

   The first atomic-resolution cryo-EM structure of the parasite ribosome resolved where L22 sits, placing it definitively within the cytoplasmic 60S large subunit rather than in any other complex.

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

   PMID:24913268

   Open questions at the time

   • L22 was not the focus and received no functional validation
   • No mutagenesis linking its position to a specific translational function
3. 2015 Medium

   Cryo-EM reconstructions from schizont-purified ribosomes confirmed L22 as a stable structural member of the translating large subunit, reinforcing its ribosomal assignment across biological samples.

   Evidence Cryo-EM reconstructions with flexible fitting of atomic models from P. falciparum schizont-purified ribosomes

   PMID:26432834

   Open questions at the time

   • No functional assay specific to L22
   • Does not distinguish L22's role from that of neighboring large-subunit proteins
4. 2025 Medium

   In situ cryo-electron tomography confirmed that L22 is a component of native, actively translating ribosomes in their cellular context, extending its structural assignment from purified particles to the intact parasite.

   Evidence In situ cryo-electron tomography of P. falciparum-infected human erythrocytes yielding eight high-resolution structures of the native ribosome in translating states

   PMID:40825879

   Open questions at the time

   • L22 not individually studied functionally
   • No perturbation to test its contribution to translation in vivo

• Whether L22 has any function beyond structural membership in the 60S subunit — including a directly demonstrated contribution to the polypeptide exit tunnel or an interaction with PfRpl4 — remains unresolved.
• No mutagenesis or knockdown of L22
• No biochemical demonstration of the predicted L22–PfRpl4 exit-tunnel interaction
• No extra-ribosomal or moonlighting role tested