Affinage · Plasmodium

PF3D7_1447000

40S ribosomal protein S5

Annotated
2026-09-08
16 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1447000 (S5) is a structural component of the 40S small ribosomal subunit of the Plasmodium falciparum 80S ribosome, present in multiple high-resolution cryo-EM structures of the assembled translating ribosome (PMID:24913268, PMID:26432834). It has been visualized as a constituent 40S protein in ribosome complexes used to define the parasite's translation machinery and its distinguishing features from mammalian ribosomes, including structures with the translation inhibitors emetine bound at the small-subunit E-site (PMID:24913268) and (+)-mefloquine bound at the GTPase-associated centre (PMID:28288098), and in in situ cryo-ET reconstructions of actively translating ribosomes inside infected erythrocytes (PMID:40825879). Beyond its membership in the 40S subunit of the P. falciparum ribosome, no specific molecular function, direct interaction, substrate, or post-translational modification has been individually demonstrated for S5/PF3D7_1447000 in the available corpus; in every structural and proteomic study it appears as a passive component of the larger ribosomal complex rather than being individually probed (PMID:40480224, PMID:34017052, PMID:41315737).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2014 Medium

    Establishing the architecture of the P. falciparum 40S subunit answered where S5 physically sits within the assembled ribosome and placed it in a drug-relevant complex.

    Evidence 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome bound to emetine at the small-subunit E-site

    PMID:24913268

    Open questions at the time
    • S5 itself is not functionally probed or mutated
    • no S5-specific interaction with emetine demonstrated
  2. 2015 Medium

    Multiple sub-nanometer reconstructions from blood-stage schizonts confirmed S5 as a stable constituent of the 40S subunit and captured dynamic states distinguishing the parasite ribosome from the mammalian one.

    Evidence Cryo-EM reconstructions with flexible-fitting atomic model building from schizont-purified ribosomes

    PMID:26432834

    Open questions at the time
    • S5 not individually functionally characterized
    • role of S5 in the observed dynamics not addressed
  3. 2017 Medium

    A drug-bound structure with mutagenesis validation confirmed the ribosome as an antimalarial target, with S5 present as a 40S component of the targeted complex.

    Evidence 3.2 Å cryo-EM of the 80S ribosome with (+)-mefloquine and site-directed mutagenesis of binding residues plus parasite resistance assay

    PMID:28288098

    Open questions at the time
    • mefloquine binds the GTPase-associated centre, not S5
    • S5 residues were not mutated
  4. 2021 Low

    Characterizing ribosome–SRP Alu domain recognition tested how the intact parasite ribosome, of which S5 is a part, engages the translation regulatory machinery.

    Evidence Cryo-EM plus NMR/SAXS binding affinity measurements of P. falciparum ribosomes with open and closed SRP Alu domains

    PMID:34017052

    Open questions at the time
    • binding is a whole-ribosome property; no S5-specific contribution shown
    • S5 not individually characterized in the interaction
  5. 2025 Medium

    In situ cryo-ET and drug-response structural studies extended the picture to actively translating ribosomes in cells, with S5 present across states of the elongation cycle.

    Evidence In situ cryo-ET of infected erythrocytes across translation states, and cryo-EM of artemisinin-treated ribosomes examining RACK1 and uS3

    PMID:40480224 PMID:40825879

    Open questions at the time
    • artemisinin/RACK1 effects centre on uS3, not S5
    • no S5-specific structural change reported
  6. 2025 Low

    Proteome-wide complex mapping across the intraerythrocytic cycle independently assigned S5 to the ribosomal protein complex and hinted at stage-dependent compositional dynamics.

    Evidence Thermal proteome profiling (MAP-X) in intact cells across seven IDC timepoints

    PMID:41315737

    Open questions at the time
    • membership inferred from co-melting profiles only
    • no functional validation specific to S5
    • stage-specific role of S5 not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether S5/PF3D7_1447000 has any function beyond structural incorporation into the 40S subunit — a direct partner, a role in mRNA/tRNA positioning, or a distinct contribution to translation regulation or drug response — remains unaddressed.
  • no S5-specific knockdown or mutation
  • no direct S5 interactor identified
  • no S5-specific post-translational modification characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Complex memberships
P. falciparum 40S small ribosomal subunitP. falciparum 80S ribosome

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved, revealing the small subunit (40S) architecture including ribosomal proteins such as S5 (PF3D7_1447000) as part of the complex bound to emetine at the E-site; emetine blocks mRNA/tRNA translocation by interacting with the small subunit E-site. Cryo-EM structure determination at 3.2 Å resolution of the P. falciparum 80S ribosome in complex with emetine eLife Medium 24913268
2015 Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution were obtained, with atomic models built by flexible fitting; S5 (PF3D7_1447000) is a constituent 40S subunit protein visualized within these structures, revealing structural and dynamic features that differentiate the P. falciparum ribosome from mammalian ribosomes. Cryo-EM reconstruction with flexible-fitting atomic model building from blood-stage schizont-purified ribosomes Nucleic acids research Medium 26432834
2017 A 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome with (+)-mefloquine bound to the GTPase-associated centre was solved; S5 (PF3D7_1447000) is a structural component of the 40S subunit present in this complex. Mutagenesis of mefloquine-binding residues generated parasites with increased resistance, confirming the ribosome as the drug target. Cryo-EM structure at 3.2 Å; site-directed mutagenesis of binding residues; parasite resistance assay Nature microbiology Medium 28288098
2025 Eight high-resolution in situ cryo-ET structures of the native P. falciparum 80S ribosome in actively translating states inside infected erythrocytes were determined; S5 (PF3D7_1447000) is a 40S subunit component present in these structures, which revealed new molecular details of the malarial translation elongation cycle and drug-induced structural changes. In situ cryo-electron tomography (cryo-ET) of P. falciparum-infected erythrocytes; high-resolution structure determination of actively translating ribosomes Nature structural & molecular biology Medium 40825879
2025 Artemisinin treatment was shown to stabilize PfRACK1 binding to the P. falciparum 80S ribosome; structural analysis revealed that the r-protein uS3 (a different 40S subunit protein) in Plasmodium has a truncated C-terminal tail compared to most eukaryotes, preventing its interaction with RACK1. S5 (PF3D7_1447000) is a 40S subunit member present in the ribosomal complex studied but is not individually characterized in this study. Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes; structural comparison of ribosomal protein uS3 C-terminal tail Structure (London, England : 1993) Low 40480224
2021 P. falciparum cytoplasmic ribosomes (containing 40S subunit components including S5/PF3D7_1447000) were shown by cryo-EM to bind both the open PfAlu domain and the closed human Alu domain of the signal recognition particle with nanomolar affinity, demonstrating non-discriminative SRP Alu domain recognition by the P. falciparum ribosome. Cryo-EM and binding affinity measurements (NMR, SAXS, cryo-EM) of P. falciparum ribosomes with SRP Alu domains Communications biology Low 34017052
2025 MAP-X (meltome-assisted profiling of protein complexes via thermal proteome profiling in intact cells) applied across seven timepoints of the P. falciparum intraerythrocytic developmental cycle predicted PF3D7_1447000 (S5) as part of the ribosomal protein complex, revealing dynamic alterations in complex composition across blood stages. Thermal proteome profiling (MAP-X) in intact P. falciparum cells across IDC timepoints; proteome-wide protein complex mapping Nature microbiology Low 41315737

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. eLife 272 24913268
2017 Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nature microbiology 136 28288098
2019 New Insights into Ribosome Structure and Function. Cold Spring Harbor perspectives in biology 48 29903714
2015 Dynamical features of the Plasmodium falciparum ribosome during translation. Nucleic acids research 45 26432834
2019 Extensions, Extra Factors, and Extreme Complexity: Ribosomal Structures Provide Insights into Eukaryotic Translation. Cold Spring Harbor perspectives in biology 26 31481454
2020 Plasmodium falciparum translational machinery condones polyadenosine repeats. eLife 21 32469313
2017 The translation elongation cycle-capturing multiple states by cryo-electron microscopy. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 20 28138066
2023 Ribosome heterogeneity and specialization of Plasmodium parasites. PLoS pathogens 13 37053161
2019 Adaptation of Translational Machinery in Malaria Parasites to Accommodate Translation of Poly-Adenosine Stretches Throughout Its Life Cycle. Frontiers in microbiology 11 31866984
2025 Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug. Nature structural & molecular biology 7 40825879
2021 Structural analysis of the SRP Alu domain from Plasmodium falciparum reveals a non-canonical open conformation. Communications biology 6 34017052
2025 Antimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome. Structure (London, England : 1993) 3 40480224
2022 Association of the receptor for activated C-kinase 1 with ribosomes in Plasmodium falciparum. The Journal of biological chemistry 3 35452681
2025 MAP-X reveals distinct protein complex dynamics across Plasmodium falciparum blood stages. Nature microbiology 2 41315737
2026 Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development. Parasites & vectors 0 42001110
2017 Parasite physiology: No longer lost in translation. Nature microbiology 0 28540920