RPL22

RPL22 (PF3D7_1467400) is a nuclear-encoded protein predicted to be targeted to the apicoplast via a bipartite N-terminal signal-plus-transit-peptide sequence (PMID:11738814), where it is modeled as a component of the apicoplast 50S ribosomal large subunit (PMID:17110371). Structural modeling places it at the polypeptide exit tunnel alongside the apicoplast-encoded PfRpl4 and the large subunit rRNA; in azithromycin-resistant P. falciparum lines (7G8 and Dd2) the PfRpl22 sequence remained unchanged while PfRpl4 acquired a G76V mutation, so RPL22 itself was not implicated as a determinant of azithromycin binding (PMID:17110371). Beyond these computational and modeling-based assignments, no direct biochemical, genetic, or structural experiment has been performed on RPL22 itself in the available corpus, and its role is established only as a predicted member of the apicoplast large ribosomal subunit.

1. 2001 Low

   To ask whether RPL22 is imported into the apicoplast, feature analysis of nuclear-encoded precursors classified it as an apicoplast-targeted protein carrying a bipartite N-terminal targeting signal.

   Evidence Computational prediction (PATS neural network, PCA, self-organizing maps) on P. falciparum protein precursors

   PMID:11738814

   Open questions at the time

   • Targeting is a computational prediction never validated experimentally by trafficking or localization assays
   • No confirmation that the encoded protein is expressed or imported
   • Cleavage site and processing of the bipartite signal not defined
2. 2006 Low

   To place RPL22 within the apicoplast ribosome and evaluate its role in azithromycin action, resistance selection and modeling assigned it to the 50S large-subunit exit tunnel but showed its sequence unchanged in resistant lines, pointing to PfRpl4 rather than RPL22 as the drug-binding determinant.

   Evidence Azithromycin resistance selection in P. falciparum 7G8 and Dd2, Sanger sequencing of loci, molecular modeling of the exit tunnel

   PMID:17110371

   Open questions at the time

   • RPL22 placement in the exit tunnel is modeling/prediction, not biochemical or structural evidence
   • No direct genetic or biochemical experiment was performed on RPL22 itself
   • Physical association of RPL22 with PfRpl4 and the large-subunit rRNA is inferred, not demonstrated

• Whether RPL22 is genuinely imported into the apicoplast, physically incorporated into the 50S subunit, and required for apicoplast ribosome function or parasite viability remains experimentally unaddressed.
• No experimental localization confirming apicoplast import
• No biochemical or structural demonstration of ribosome incorporation
• No knockout/knockdown establishing an essential or dispensable role