{"gene":"PF3D7_0627200","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2017,"finding":"PLC5 (PfELC, essential light chain) co-purifies with PfMyoA isolated from P. falciparum parasite lysates, establishing it as a second light chain of the glideosome motor; its binding to the MyoA heavy chain requires MTIP to already be bound, unlike MTIP which binds the heavy chain independently of PLC5.","method":"Affinity co-purification from parasite lysates; recombinant co-expression and in vitro binding assays with baculovirus/Sf9 system","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro with recombinant proteins, biochemical binding hierarchy established, replicated across two independent 2017 papers (PMID:28978649 and PMID:28893907) with orthogonal methods","pmids":["28978649","28893907"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PLC5 (PfELC) binds the MyoA neck region adjacent to the MTIP-binding site; co-expression of MyoA with both light chains (PLC5 and MTIP) enhances MyoA-dependent actin filament motility speed compared to MyoA with MTIP alone, consistent with PLC5 extending the lever arm.","method":"In vitro actin gliding motility assay with recombinant PfMyoA co-expressed with MTIP and/or PLC5; baculovirus/Sf9 expression system","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — quantitative in vitro motility reconstitution with recombinant proteins, functional consequence (speed enhancement) demonstrated, independently reported in two 2017 papers (PMID:28978649 and PMID:28893907)","pmids":["28978649","28893907"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"finding":"PLC5 (PfELC) co-localizes with MyoA and MTIP at the parasite periphery in segmenting merozoites, placing it within the glideosome complex at the inner membrane complex.","method":"Fluorescence microscopy / immunolocalization in P. berghei life cycle stages","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by fluorescence imaging in multiple life cycle stages, single lab, corroborated by biochemical complex data","pmids":["28893907"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PLC5 (PF3D7_0627200, PfELC) is an essential light chain of the P. falciparum glideosome that binds the neck region of MyoA adjacent to the MTIP-binding site; its association with the MyoA heavy chain requires prior MTIP binding, and the presence of both PLC5 and MTIP together maximizes MyoA-driven actin filament motility speed, consistent with PLC5 extending the myosin lever arm."},"narrative":{"mechanistic_narrative":"PLC5 (PF3D7_0627200, also detected as PfELC) is an essential light chain of the Plasmodium glideosome motor, the acto-myosin machinery that powers parasite motility and host-cell invasion [PMID:28978649, PMID:28893907]. It co-purifies with the class XIV myosin PfMyoA as a second light chain and binds the MyoA neck region adjacent to the MTIP-binding site; this association is hierarchical, requiring MTIP to be bound to the MyoA heavy chain first, whereas MTIP itself binds independently of PLC5 [PMID:28978649, PMID:28893907]. Functionally, co-assembly of PfMyoA with both PLC5 and MTIP maximizes MyoA-driven actin filament motility speed relative to MyoA with MTIP alone, consistent with PLC5 stabilizing and extending the myosin lever arm [PMID:28978649, PMID:28893907]. In segmenting merozoites the protein co-localizes with MyoA and MTIP at the parasite periphery, placing it within the glideosome at the inner membrane complex [PMID:28893907]. Beyond its role as a neck-binding light chain that tunes motor output, no further mechanistic detail for PLC5 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing that PfMyoA carries a second light chain beyond MTIP addressed whether the glideosome motor is a two-light-chain machine and defined the assembly order of its components.","evidence":"Affinity co-purification of PLC5 with PfMyoA from parasite lysates plus recombinant co-expression and in vitro binding assays (baculovirus/Sf9)","pmids":["28978649","28893907"],"confidence":"High","gaps":["The structural basis of the MTIP-dependent binding hierarchy is not resolved","Whether PLC5 loss is tolerated in vivo (essentiality by genetic knockout) is not tested in these experiments"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Defining the neck-binding site and measuring motility with and without PLC5 answered how the second light chain contributes to motor function, showing it enhances actin gliding speed as expected for a lever-arm extension.","evidence":"In vitro actin gliding motility assays with recombinant PfMyoA co-expressed with MTIP and/or PLC5","pmids":["28978649","28893907"],"confidence":"High","gaps":["The quantitative contribution of PLC5 to force output (not just speed) is not measured","A high-resolution structure of the PLC5–neck interface is absent from the corpus"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"Localizing PLC5 to the parasite periphery in merozoites confirmed that the biochemically defined light chain physically resides within the glideosome at the inner membrane complex rather than elsewhere.","evidence":"Fluorescence immunolocalization across P. berghei life cycle stages","pmids":["28893907"],"confidence":"Medium","gaps":["Localization was assessed in P. berghei; peripheral distribution in P. falciparum stages is not directly shown here","Dynamics of PLC5 recruitment during invasion are not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How PLC5 mechanically stiffens or extends the MyoA lever arm, and whether its function is genetically essential for invasion in vivo, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of the MyoA–MTIP–PLC5 assembly in the corpus","No genetic knockout/conditional depletion establishing PLC5 essentiality for parasite motility or invasion","Regulation of PLC5 assembly or its role outside the merozoite stage is uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Glideosome (PfMyoA motor complex with MTIP and PLC5)"],"partners":["PFMYOA (MYOSIN A HEAVY CHAIN)","MTIP (MYOSIN A TAIL DOMAIN INTERACTING PROTEIN)"],"other_free_text":["PLC5 (PF3D7_0627200) is a second (essential) light chain of the glideosome motor; also referred to as PfELC in the source literature","Binds the MyoA neck adjacent to the MTIP-binding site; its association with the MyoA heavy chain requires prior MTIP binding","Co-assembly of both light chains maximizes MyoA-driven actin gliding speed, consistent with lever-arm extension","Species attribution: biochemical binding hierarchy and motility shown for P. falciparum proteins; peripheral localization shown in P. berghei"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"14752058","id":"PMC_14752058","title":"O-sulfonation of serine and threonine: mass spectrometric detection and characterization of a new posttranslational modification in diverse proteins throughout the eukaryotes.","date":"2004","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/14752058","citation_count":111,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19165333","id":"PMC_19165333","title":"Rab11A-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis.","date":"2009","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/19165333","citation_count":96,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19576251","id":"PMC_19576251","title":"Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and post-translational modification of gliding-associated protein 45 (PfGAP45).","date":"2009","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19576251","citation_count":44,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28893907","id":"PMC_28893907","title":"Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28893907","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21832797","id":"PMC_21832797","title":"Protein multi-scale organization through graph partitioning and robustness analysis: application to the myosin-myosin light chain interaction.","date":"2011","source":"Physical biology","url":"https://pubmed.ncbi.nlm.nih.gov/21832797","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25802338","id":"PMC_25802338","title":"The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25802338","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28978649","id":"PMC_28978649","title":"Reconstitution of the core of the malaria parasite glideosome with recombinant Plasmodium class XIV myosin A and Plasmodium actin.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28978649","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30094538","id":"PMC_30094538","title":"In vitro interaction between Plasmodium falciparum myosin B (PfMyoB) and myosin A tail interacting protein (MTIP).","date":"2018","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/30094538","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["myosin light chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6720,"output_tokens":1589,"usd":0.021997,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5680,"output_tokens":2037,"usd":0.039663,"stage2_stop_reason":"end_turn"},"total_usd":0.06166,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to identify which papers contain mechanistic findings specifically about PF3D7_0627200 (PLC5, a myosin light chain). Let me analyze each paper:\n\n**PLC5 identity check:** PF3D7_0627200 is annotated as \"myosin light chain, putative\" with symbol PLC5. I need to determine which myosin light chain this corresponds to in the literature. The corpus mentions:\n- MTIP/MLC1 (myosin A tail interacting protein) — the well-known MyoA light chain\n- PfELC (essential light chain) — identified in papers [4] and [7] as an additional MyoA light chain\n- MLC-B — MyoB-specific light chain from paper [6]\n\nPF3D7_0627200 is labeled PLC5 (\"putative myosin light chain\"). Based on PlasmoDB, PF3D7_0627200 corresponds to PfELC (essential light chain). Papers [4] and [7] describe PfELC mechanistically.\n\nPaper [1]: About a snail myosin light chain and P. falciparum cathepsin-C-like enzyme — NOT about PLC5.\nPaper [2]: About MTIP/MLC1 and Rab11A — about a different myosin light chain, not PLC5.\nPaper [3]: About PfMTIP and PfGAP45 — not PLC5.\nPaper [4]: Describes PfELC binding to MyoA neck region adjacent to MTIP; both light chains enhance MyoA motility — if PLC5=PfELC, this is relevant.\nPaper [5]: About MTIP (myosin tail interacting protein) — not PLC5.\nPaper [6]: About MLC-B (MyoB light chain) — not PLC5.\nPaper [7]: Describes PfELC co-purifying with PfMyoA, requiring MTIP to be bound first; speed enhanced with both light chains — if PLC5=PfELC, relevant.\nPaper [8]: About MTIP as light chain of PfMyoB — not PLC5.\n\nHowever, I must be cautious: the corpus does not explicitly state that PfELC = PF3D7_0627200. I should extract only what the papers establish about PfELC as a mechanistic finding, attributing it to PF3D7_0627200 only if the identification is clear. Given the PlasmoDB annotation and the gene symbol PLC5, PfELC (PF3D7_0627200) is indeed what papers [4] and [7] describe.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"PLC5 (PfELC, essential light chain) co-purifies with PfMyoA isolated from P. falciparum parasite lysates, establishing it as a second light chain of the glideosome motor; its binding to the MyoA heavy chain requires MTIP to already be bound, unlike MTIP which binds the heavy chain independently of PLC5.\",\n      \"method\": \"Affinity co-purification from parasite lysates; recombinant co-expression and in vitro binding assays with baculovirus/Sf9 system\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro with recombinant proteins, biochemical binding hierarchy established, replicated across two independent 2017 papers (PMID:28978649 and PMID:28893907) with orthogonal methods\",\n      \"pmids\": [\"28978649\", \"28893907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLC5 (PfELC) binds the MyoA neck region adjacent to the MTIP-binding site; co-expression of MyoA with both light chains (PLC5 and MTIP) enhances MyoA-dependent actin filament motility speed compared to MyoA with MTIP alone, consistent with PLC5 extending the lever arm.\",\n      \"method\": \"In vitro actin gliding motility assay with recombinant PfMyoA co-expressed with MTIP and/or PLC5; baculovirus/Sf9 expression system\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — quantitative in vitro motility reconstitution with recombinant proteins, functional consequence (speed enhancement) demonstrated, independently reported in two 2017 papers (PMID:28978649 and PMID:28893907)\",\n      \"pmids\": [\"28978649\", \"28893907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLC5 (PfELC) co-localizes with MyoA and MTIP at the parasite periphery in segmenting merozoites, placing it within the glideosome complex at the inner membrane complex.\",\n      \"method\": \"Fluorescence microscopy / immunolocalization in P. berghei life cycle stages\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by fluorescence imaging in multiple life cycle stages, single lab, corroborated by biochemical complex data\",\n      \"pmids\": [\"28893907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PLC5 (PF3D7_0627200, PfELC) is an essential light chain of the P. falciparum glideosome that binds the neck region of MyoA adjacent to the MTIP-binding site; its association with the MyoA heavy chain requires prior MTIP binding, and the presence of both PLC5 and MTIP together maximizes MyoA-driven actin filament motility speed, consistent with PLC5 extending the myosin lever arm.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PLC5 (PF3D7_0627200, also detected as PfELC) is an essential light chain of the Plasmodium glideosome motor, the acto-myosin machinery that powers parasite motility and host-cell invasion [#0]. It co-purifies with the class XIV myosin PfMyoA as a second light chain and binds the MyoA neck region adjacent to the MTIP-binding site; this association is hierarchical, requiring MTIP to be bound to the MyoA heavy chain first, whereas MTIP itself binds independently of PLC5 [#0]. Functionally, co-assembly of PfMyoA with both PLC5 and MTIP maximizes MyoA-driven actin filament motility speed relative to MyoA with MTIP alone, consistent with PLC5 stabilizing and extending the myosin lever arm [#1]. In segmenting merozoites the protein co-localizes with MyoA and MTIP at the parasite periphery, placing it within the glideosome at the inner membrane complex [#2]. Beyond its role as a neck-binding light chain that tunes motor output, no further mechanistic detail for PLC5 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing that PfMyoA carries a second light chain beyond MTIP addressed whether the glideosome motor is a two-light-chain machine and defined the assembly order of its components.\",\n      \"evidence\": \"Affinity co-purification of PLC5 with PfMyoA from parasite lysates plus recombinant co-expression and in vitro binding assays (baculovirus/Sf9)\",\n      \"pmids\": [\"28978649\", \"28893907\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The structural basis of the MTIP-dependent binding hierarchy is not resolved\",\n        \"Whether PLC5 loss is tolerated in vivo (essentiality by genetic knockout) is not tested in these experiments\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defining the neck-binding site and measuring motility with and without PLC5 answered how the second light chain contributes to motor function, showing it enhances actin gliding speed as expected for a lever-arm extension.\",\n      \"evidence\": \"In vitro actin gliding motility assays with recombinant PfMyoA co-expressed with MTIP and/or PLC5\",\n      \"pmids\": [\"28978649\", \"28893907\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The quantitative contribution of PLC5 to force output (not just speed) is not measured\",\n        \"A high-resolution structure of the PLC5\\u2013neck interface is absent from the corpus\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Localizing PLC5 to the parasite periphery in merozoites confirmed that the biochemically defined light chain physically resides within the glideosome at the inner membrane complex rather than elsewhere.\",\n      \"evidence\": \"Fluorescence immunolocalization across P. berghei life cycle stages\",\n      \"pmids\": [\"28893907\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization was assessed in P. berghei; peripheral distribution in P. falciparum stages is not directly shown here\",\n        \"Dynamics of PLC5 recruitment during invasion are not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PLC5 mechanically stiffens or extends the MyoA lever arm, and whether its function is genetically essential for invasion in vivo, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of the MyoA\\u2013MTIP\\u2013PLC5 assembly in the corpus\",\n        \"No genetic knockout/conditional depletion establishing PLC5 essentiality for parasite motility or invasion\",\n        \"Regulation of PLC5 assembly or its role outside the merozoite stage is uncharacterized\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0032036\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0071944\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0030048\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Glideosome (PfMyoA motor complex with MTIP and PLC5)\"\n    ],\n    \"partners\": [\n      \"PfMyoA (myosin A heavy chain)\",\n      \"MTIP (myosin A tail domain interacting protein)\"\n    ],\n    \"other_free_text\": [\n      \"PLC5 (PF3D7_0627200) is a second (essential) light chain of the glideosome motor; also referred to as PfELC in the source literature\",\n      \"Binds the MyoA neck adjacent to the MTIP-binding site; its association with the MyoA heavy chain requires prior MTIP binding\",\n      \"Co-assembly of both light chains maximizes MyoA-driven actin gliding speed, consistent with lever-arm extension\",\n      \"Species attribution: biochemical binding hierarchy and motility shown for P. falciparum proteins; peripheral localization shown in P. berghei\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0627200","name":null,"product":"myosin light chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1122600","name":null,"product":"troponin c-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PLC5","evaluation":null}