rpl4

PBANKA_API00430 (rpl4) is inferred, from evidence in Plasmodium falciparum, to encode an apicoplast-encoded 50S ribosomal protein L4 that contributes to the polypeptide exit tunnel of the apicoplast ribosome, the site targeted by azithromycin (PMID:17110371). In azithromycin-resistant P. falciparum lines a G76V mutation in rpl4 was identified, and molecular modeling indicates this substitution reorients the neighboring L75 side chain in a way that would preclude azithromycin from occupying the exit tunnel, implicating rpl4 directly in the drug-binding architecture of the apicoplast 50S ribosome (PMID:17110371). Beyond this resistance-mapping and modeling evidence — including the computationally inferred association of rpl4 with PfRpl22 and large-subunit rRNA to form the exit tunnel (PMID:17110371) — no direct biochemical characterization of rpl4 has been established in the available corpus, and all findings derive from P. falciparum rather than the subject P. berghei gene itself.

1. 2006 Medium

   Whether azithromycin acts on the apicoplast translation machinery was addressed by mapping resistance to a specific ribosomal protein, establishing rpl4 as part of the drug's target.

   Evidence In vitro resistance selection with Sanger sequencing of resistant P. falciparum lines plus molecular modeling of mutant PfRpl4 with azithromycin

   PMID:17110371

   Open questions at the time

   • No mutagenesis complementation or in vitro reconstitution confirms G76V is causative for resistance
   • The modeled altered L75 orientation is not experimentally validated by structure
   • Findings are in P. falciparum; the P. berghei ortholog PBANKA_API00430 was not directly tested
2. 2006 Low

   The structural context of rpl4 was addressed by predicting its assembly with PfRpl22 and large-subunit rRNA into the 50S polypeptide exit tunnel, framing rpl4 as a tunnel-forming component rather than a standalone drug target.

   Evidence Structural modeling and sequence analysis in P. falciparum

   PMID:17110371

   Open questions at the time

   • Complex membership is inferred from computational modeling and homology only, with no biochemical reconstitution
   • Direct interaction between rpl4 and PfRpl22 or rRNA is not demonstrated
   • No evidence addresses complex assembly for PBANKA_API00430 itself

• Whether PBANKA_API00430 in P. berghei forms the apicoplast 50S exit tunnel, binds azithromycin, and carries the same resistance liability remains uncharacterized in the available corpus.
• No direct functional, biochemical, or genetic data on PBANKA_API00430
• No experimental validation of exit-tunnel assembly or drug binding in any species
• No structural determination of the apicoplast 50S ribosome