SRP9

PF3D7_0729000 (SRP9) is a subunit of the six-polypeptide P. falciparum signal recognition particle, which assembles with a 303 nt SRP RNA to mediate co-translational protein targeting (PMID:24434517). Within this complex, SRP9 partners with SRP14 and Alu RNA to form the Alu domain, which in P. falciparum adopts a non-canonical open Y-shaped conformation rather than the closed loop-loop pseudoknot of human and prokaryotic counterparts; despite this open geometry, the domain binds cytoplasmic P. falciparum ribosomes with nanomolar affinity, a species-specific recognition not reproduced by human ribosomes (PMID:34017052). In parasites, SRP9-GFP shows nucleo-cytoplasmic distribution, and its nuclear import depends on the importin α/β pathway, since the import inhibitor ivermectin blocks nuclear entry of SRP polypeptides including SRP9 at submicromolar concentrations and kills the parasite (PMID:24434517). Beyond its role in the SRP Alu domain and its shuttling behavior, no further gene-specific mechanistic detail for SRP9 has been characterized in the available corpus.

1. 2014 Medium

   Establishing that SRP9 is a bona fide constituent of the parasite SRP and defining its subcellular trafficking answered whether this subunit functions within the P. falciparum SRP and how it reaches its site of action.

   Evidence Transgenic parasites expressing SRP9-GFP with co-localization microscopy and pharmacological nuclear-import inhibition by ivermectin

   PMID:24434517

   Open questions at the time

   • Does not resolve which cargo or targeting events SRP9 specifically supports
   • Killing by ivermectin is not specific to SRP9 and does not isolate its individual contribution
   • No direct demonstration of SRP9 function in co-translational targeting
2. 2021 High

   Determining the structure of the SRP9/14-Alu RNA domain resolved whether the parasite Alu domain shares the conserved closed architecture and how it engages ribosomes, revealing a divergent open conformation with species-selective ribosome binding.

   Evidence NMR, SAXS, and cryo-EM structural analysis of the Alu domain with ribosome-binding affinity measurements

   PMID:34017052

   Open questions at the time

   • Does not isolate the individual contribution of SRP9 versus SRP14 to the open conformation or ribosome binding
   • Functional consequence of the open geometry for translation retardation in living parasites not demonstrated
   • Structural basis of the P. falciparum ribosome selectivity not defined at residue level

• The specific molecular role of SRP9 within the Alu domain, its individual contribution to ribosome binding and translation retardation, and any function outside the SRP complex remain undefined.
• No subunit-resolved dissection of SRP9 within the Alu heterodimer
• No direct evidence linking SRP9 to translation elongation arrest in vivo
• No characterization of SRP9 function independent of the SRP complex