Affinage · Plasmodium

P113

PF3D7_1420700 · surface protein P113

Annotated
2026-09-08
17 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P113 (PF3D7_1420700) is a GPI-anchored Plasmodium surface protein that functions across the merozoite surface and the parasitophorous vacuole, and additionally supports pre-erythrocytic development (PMID:28186186, PMID:35403274, PMID:17553576). At the merozoite surface it directly binds the N-terminal region of PfRH5 through a two-domain, rhamnose-binding-lectin-like region, thereby tethering the secreted RH5 invasion complex to the parasite surface in a releasable manner (PMID:28186186, PMID:32900802). Independently of blood-stage growth, P113 also localizes within the parasitophorous vacuole and at the plasma membrane, where it co-purifies with the PTEX export machinery and EPIC and is required to maintain normal parasitophorous vacuole membrane architecture (PMID:35403274). During schizont maturation P113 is proteolytically processed from a ~113 kDa precursor into smaller products (PMID:3309058), and in P. berghei it is expressed in sporozoites under SLARP control and supports efficient sporozoite-to-liver-stage conversion (PMID:24657782). Antibodies that block the P113–RH5 interface do not inhibit blood-stage growth, and the precise mechanistic contribution of P113 to invasion versus vacuole maintenance is not resolved in the available corpus (PMID:32900802, PMID:35403274).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1987 Medium

    Establishing that a 113 kDa antigen exists at the schizont/merozoite surface and vacuolar space and is proteolytically matured set the earliest foundation for P113 as a stage-specific surface/vacuolar protein.

    Evidence Monoclonal antibody localization, immunoelectron microscopy, and pulse-chase metabolic labeling in P. falciparum

    PMID:3309058

    Open questions at the time
    • Function of the processing products unknown
    • No molecular identity of interacting partners at this stage
    • Purpose of vacuolar versus surface localization unresolved
  2. 2007 Medium

    Identifying P113 as an abundant, high-molecular-weight, DRM-associated putative GPI-anchored protein reframed it as a component of large merozoite surface complexes.

    Evidence Detergent-resistant membrane purification, blue native-PAGE, and mass spectrometry in P. falciparum schizonts

    PMID:17553576

    Open questions at the time
    • Complex composition not defined
    • GPI anchoring inferred, not directly demonstrated
    • Functional role of complex assembly unknown
  3. 2010 Medium

    Mapping P113 peptides that bind red blood cells implicated the protein directly in the invasion process rather than being a passive surface antigen.

    Evidence Synthetic peptide RBC binding, receptor characterization on enzyme-treated RBCs, cross-linking, and invasion inhibition assays in P. falciparum

    PMID:20411955

    Open questions at the time
    • Peptide binding not validated by genetic loss-of-function
    • RBC receptor identity not established
    • Relationship of HABP binding to native protein function unclear
  4. 2014 Medium

    Gene deletion in P. berghei revealed a second, pre-erythrocytic role, showing P113 is dispensable for blood-stage growth but required for efficient sporozoite-to-liver-stage conversion under SLARP control.

    Evidence Targeted gene deletion, in vivo pre-erythrocytic development and sporozoite conversion assays, and expression analysis in P. berghei

    PMID:24657782

    Open questions at the time
    • Molecular mechanism of the sporozoite conversion defect unknown
    • Whether P. falciparum P113 has an analogous liver-stage role untested
    • Downstream SLARP-regulated pathway not defined
  5. 2017 High

    Discovery that P113 directly binds the RH5 N-terminus provided a mechanistic model for how the secreted RH5 invasion complex is releasably tethered to the merozoite surface.

    Evidence Recombinant protein production and AVEXIS interaction assays with binding-interdependency mapping of the RH5 complex in P. falciparum

    PMID:28186186

    Open questions at the time
    • In vivo requirement of the P113–RH5 tether not demonstrated by loss-of-function
    • How release from the surface is regulated unknown
    • Stoichiometry within the surface complex undefined
  6. 2020 High

    Structural and mutagenesis definition of the RH5-binding region resolved the P113–RH5 interface at atomic level but showed that blocking it is not sufficient to inhibit blood-stage growth.

    Evidence X-ray crystallography (Fab-chaperone), HDX-MS, site-directed mutagenesis, and monoclonal antibody growth-inhibition assays in P. falciparum

    PMID:32900802

    Open questions at the time
    • Why interface-blocking antibodies fail to inhibit growth unexplained
    • Functional necessity of the interaction for invasion unresolved
    • Structure covers only the RH5-binding region
  7. 2021 Medium

    Detection of a processed P113 form within a stable EXP2-containing translocation intermediate suggested involvement in export of integral membrane proteins across the PV membrane.

    Evidence Immunofluorescence, inducible translocon-clogging with mini-SURFIN4.1, and co-immunoprecipitation of the intermediate complex in P. falciparum

    PMID:33901679

    Open questions at the time
    • Role inferred from association, not proven by loss-of-function
    • Single Co-IP/pulldown context
    • Contribution of the processed form versus full-length undefined
  8. 2022 High

    Localization to the PV with PTEX/EPIC and a knockdown phenotype of disrupted PVM morphology defined a distinct vacuolar structural role for P113 separate from its surface invasion function.

    Evidence Affinity pulldown with MS, conditional knockdown, partial gene deletion, protein export assays, and PVM morphology microscopy in P. falciparum

    PMID:35403274

    Open questions at the time
    • Molecular basis of PVM maintenance unknown
    • Whether PTEX/EPIC association is direct or bridged unresolved
    • How the surface RH5-tether and PV roles are reconciled unclear
  9. 2025 Medium

    A high-resolution structure of a helical domain of P113 extended structural coverage beyond the RH5-binding region and nominated candidate residues for binding another parasite protein.

    Evidence 1.7 Å X-ray crystallography, size-exclusion chromatography, and computational (AlphaFold/STRING) interaction mapping in P. falciparum

    PMID:40192714

    Open questions at the time
    • PF3D7_0308000 interaction predicted computationally, not validated in vitro
    • Key residues not tested by mutagenesis
    • Functional role of the helical domain undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How P113's surface RH5-tethering function, its parasitophorous vacuole membrane maintenance role, and its pre-erythrocytic function are mechanistically integrated within one protein remains unresolved.
  • No unified loss-of-function model linking surface and PV roles
  • Direct requirement of the P113–RH5 interaction for invasion untested
  • Molecular mechanism of PVM architecture maintenance unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
EXP2PF3D7_0308000 (COMPUTATIONALLY PREDICTED)PFRH5 (N-TERMINAL REGION)
Complex memberships
EPIC (exported protein-interacting complex)EXP2-containing translocation intermediate complexHigh-molecular-weight DRM merozoite surface complexesPTEX (Plasmodium Translocon of Exported Proteins)RH5 invasion complex (via direct RH5 N-terminus binding)

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 P113 is a merozoite surface protein that directly binds the N-terminal region (RH5Nt) of PfRH5 via a protein–protein interaction established using recombinant proteins and a sensitive protein interaction assay. This interaction provides a releasable mechanism for anchoring the secreted RH5 complex to the merozoite surface. Recombinant protein production, sensitive cell-based protein interaction assay (AVEXIS), binding interdependency mapping of RH5 complex components Nature Communications High 28186186
2020 The crystal structure of the RH5-binding region of P113 was determined (using a Fab fragment as crystallization chaperone) and shown to comprise two domains with structural similarity to rhamnose-binding lectins. The RH5 binding site on P113 was mapped using hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis. A monoclonal antibody that bound this interface and inhibited the P113–RH5 interaction did not inhibit parasite blood-stage growth. X-ray crystallography (Fab-chaperone method), hydrogen-deuterium exchange mass spectrometry (HDX-MS), site-directed mutagenesis, monoclonal antibody binding/inhibition assays, parasite growth inhibition assay mBio High 32900802
2022 P113 localizes within the parasitophorous vacuole (PV) and at the parasite plasma membrane, and co-purifies (via pulldown from in vitro cultures) with components of the Plasmodium Translocon of Exported Proteins (PTEX) and the exported protein-interacting complex (EPIC). Genetic knockdown or partial deletion of P113 did not significantly reduce parasite growth or protein export but disrupted parasitophorous vacuole membrane (PVM) morphology, indicating P113 plays a role in maintaining normal PVM architecture. Affinity pulldown/co-immunoprecipitation from P. falciparum cultures (mass spectrometry identification of binding partners), conditional genetic knockdown, partial gene deletion, microscopic assessment of PVM morphology, protein export assays Molecular Microbiology High 35403274
2021 P113 localizes in dense granules at the merozoite stage and on the parasite periphery after red blood cell invasion. Using an inducible translocon-clogged mini-SURFIN4.1 system, P113 (a processed form) was found in a stable translocation intermediate complex at the parasite plasma membrane together with EXP2, suggesting a potential role for P113 in translocation of integral membrane proteins across the PV membrane. Immunofluorescence localization, inducible translocon-clogging assay, co-immunoprecipitation/pulldown of translocation intermediate complex, western blot detection of processed P113 form Parasitology International Medium 33901679
2014 In Plasmodium berghei, targeted gene deletion of P113 produced viable blood-stage parasites with no blood-stage growth defect, but p113-null sporozoites displayed reduced sporozoite-to-liver-stage conversion in vivo and lower merozoite output, without delaying liver stage development. Pre-erythrocytic expression of P113 is controlled by the liver stage master regulator SLARP, a hallmark of UIS (upregulated in infectious sporozoites) genes. Targeted gene deletion in P. berghei, in vitro and in vivo pre-erythrocytic development assays, xeno-diagnostic test for sporozoite conversion, RT-PCR/expression analysis for SLARP regulation Molecular and Biochemical Parasitology Medium 24657782
2007 P113 (referred to as Pf113 in the abstract) was identified as one of the most abundant proteins in detergent-resistant membranes (DRMs) of P. falciparum schizonts, predominating in high molecular weight species by blue native-PAGE, suggesting its assembly into large complexes at the merozoite surface. P113 is a putative GPI-anchored protein. Detergent-resistant membrane purification, blue native-PAGE, mass spectrometry protein identification Molecular and Biochemical Parasitology Medium 17553576
2010 Peptides derived from P113 (Pf113) were identified as high-activity binding peptides (HABPs) that bind red blood cells with a large number of binding sites per RBC. Enzyme treatment of RBCs and cross-linking assays were used to characterize the nature of surface receptors. Invasion inhibition and immunofluorescence studies indicated that P113 is involved in RBC invasion and that its adhesion to RBCs is mediated by these HABPs. Synthetic peptide RBC binding assays, enzyme-treated RBC receptor characterization, chemical cross-linking, invasion inhibition assays, immunofluorescence Journal of Medicinal Chemistry Medium 20411955
1987 A 113-kDa antigen (p113) identified by monoclonal antibody 5E3 is localized at the surface of schizonts, in the vacuolar space, and at the surface of merozoites before release. In pulse-chase experiments, p113 is processed to 100-, 70-, 55-, and 50-kDa products. The protein is synthesized by mature trophozoites and young schizonts and is released into culture medium upon schizont rupture but accumulates in immune complexes in the presence of immune serum. Monoclonal antibody characterization, immunofluorescence/immunoelectron microscopy, pulse-chase metabolic labeling, immunoblot of immune complexes Journal of Immunology Medium 3309058
2025 The crystal structure of a helical-rich domain of P113 (residues 311–679) was determined at 1.7 Å resolution, revealing a predominantly α-helical composition with two left-handed orthogonal four-helix bundles connected by a disordered region; the protein was confirmed monomeric in solution. Key residues (Asp475, Arg381, Lys386, Asn390, Asp392, Lys533) were identified as critical interaction sites for binding PF3D7_0308000. X-ray crystallography (1.7 Å resolution), size exclusion chromatography (monomer confirmation), protein-protein interaction analysis (STRING/AlphaFold predictions for interaction mapping) Acta Crystallographica Section D Medium 40192714

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 New antigens for a multicomponent blood-stage malaria vaccine. Science translational medicine 142 25080477
2007 Identification of protein complexes in detergent-resistant membranes of Plasmodium falciparum schizonts. Molecular and biochemical parasitology 73 17553576
1987 Monoclonal antibody characterization of Plasmodium falciparum antigens in immune complexes formed when schizonts rupture in the presence of immune serum. Journal of immunology (Baltimore, Md. : 1950) 70 3309058
2017 P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5. Nature communications 59 28186186
2018 Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria. PloS one 33 29883485
2023 Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria. Science translational medicine 30 36753561
2021 The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations. Malaria journal 21 34162366
2022 The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture. Molecular microbiology 16 35403274
2023 Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex in Plasmodium falciparum parasite population in selected malaria-endemic regions, Kenya. Frontiers in tropical diseases 12 38406638
2010 Conserved high activity binding peptides are involved in adhesion of two detergent-resistant membrane-associated merozoite proteins to red blood cells during invasion. Journal of medicinal chemistry 12 20411955
2014 The Plasmodium protein P113 supports efficient sporozoite to liver stage conversion in vivo. Molecular and biochemical parasitology 11 24657782
2021 Plasmodium falciparum SURFIN4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red blood cell. Parasitology international 9 33901679
2020 The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site. mBio 8 32900802
2016 Comparative Antibody Responses Against three Antimalarial Vaccine Candidate Antigens from Urban and Rural Exposed Individuals in Gabon. European journal of microbiology & immunology 6 27980857
2017 High Level of Specific Anti-Plasmodium Falciparum Merozoite IgG1 Antibodies in Rural Asymptomatic Individuals of Dienga, South-Eastern Gabon. European journal of microbiology & immunology 2 29403652
2016 Immunoglobulin response to the low polymorphic Pf113 antigen in children from Lastoursville, South-East of Gabon. Acta tropica 2 27523305
2025 The crystal structure of an uncharacterized domain of P113 from Plasmodium falciparum. Acta crystallographica. Section D, Structural biology 0 40192714