SRP19

PF3D7_1216300 (SRP19) is a constituent of the Plasmodium falciparum signal recognition particle (SRP), a ribonucleoprotein complex comprising SRP9, SRP14, SRP54, SRP68, SRP72 and a 303 nt SRP RNA (PMID:24434517). Within this assembly, SRP19 belongs to the S domain — together with SRP54 and SRP68/72 — which is responsible for signal recognition and receptor targeting, as distinct from the Alu domain (PMID:34017052). In vivo co-localization in asexual blood stages demonstrates association of SRP19 with SRP9/14 and SRP54, confirming assembly of the PfSRP complex in the parasite (PMID:34017052). An SRP19-GFP chimera shows nucleo-cytoplasmic localization in asexual blood stages, and nuclear import of SRP19 (and other PfSRP polypeptides) is blocked by the importin α/β inhibitor ivermectin at submicromolar concentrations, which kills parasites (PMID:24434517). Beyond its assignment to the SRP complex and S domain and this shuttling behavior, no SRP19-specific molecular mechanism has been reconstituted or characterized in the available corpus.

1. 2014 Medium

   Establishing that SRP19 is a genuine component of the parasite SRP and that its nuclear import can be pharmacologically disrupted linked an SRP subunit to a druggable trafficking step in the parasite.

   Evidence SRP19-GFP transgenic parasite lines with co-localization microscopy and ivermectin inhibition in P. falciparum asexual blood stages

   PMID:24434517

   Open questions at the time

   • The specific molecular activity of SRP19 within the complex was not assayed directly
   • Whether ivermectin killing is mechanistically attributable to SRP19 import loss specifically, versus general PfSRP disruption, is not resolved
   • The functional role of nucleo-cytoplasmic shuttling for a canonically cytoplasmic SRP subunit is not defined
2. 2019 Low

   Large-scale interactome profiling placed SRP19 in a defined protein cluster, providing native-complex evidence consistent with its complex membership but no SRP19-directed mechanism.

   Evidence Blue native-PAGE with quantitative mass spectrometry and machine-learning interaction prediction in P. falciparum schizonts

   PMID:31390575

   Open questions at the time

   • Pan-interactome catalog with no experiment performed specifically on SRP19
   • Cluster membership does not establish direct binding partners for SRP19
3. 2021 Medium

   Domain assignment resolved SRP19 to the S domain of the PfSRP responsible for signal recognition and receptor targeting, distinguishing its functional context from the Alu domain.

   Evidence Structural study focused on the Alu domain (cryo-EM/NMR/SAXS) referencing prior in vivo co-localization of SRP19 with SRP9/14 and SRP54 in P. falciparum asexual blood stages

   PMID:34017052

   Open questions at the time

   • The paper did not reconstitute or structurally resolve SRP19 itself
   • Direct demonstration of SRP19's contribution to signal recognition in the parasite is absent

• The SRP19-specific molecular function — its RNA-binding and role in assembling or stabilizing the S domain and enabling co-translational ER targeting in P. falciparum — remains uncharacterized experimentally.
• No reconstitution of SRP19 activity or direct binding assay in the corpus
• No genetic knockout/knockdown phenotype for SRP19 specifically
• No structural model of SRP19 within the PfSRP