{"gene":"PF3D7_1118700","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2015,"finding":"MLC-B (PF3D7_1118700) was identified as a MyoB-specific light chain in P. falciparum; it contains a calmodulin-like domain at its C terminus and an extended N-terminal region, localizes to the extreme apical pole of merozoites co-incident with MyoB, and forms a complex with MyoB as shown by co-immunoprecipitation. MLC-B does not associate with glideosome complex proteins (e.g., MTIP).","method":"Co-immunoprecipitation, immunofluorescence localization, domain analysis across P. falciparum, P. berghei, and P. knowlesi","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and direct localization with functional interpretation, single lab, two orthogonal methods","pmids":["25802338"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium knowlesi","strain":""}]},{"year":2022,"finding":"In P. falciparum, MLC-B (PF3D7_1118700) binds to the MyoB IQ2 motif in vitro, as established by biochemical/biophysical binding assays using purified recombinant proteins; additionally, four other putative regulatory light chains were found to bind the same MyoB IQ2 motif in vitro.","method":"Biochemical and biophysical binding assays (in vitro), small-angle X-ray scattering for low-resolution structure","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro reconstituted binding assay with purified recombinant proteins and biophysical characterization, single lab","pmids":["36273584"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"In P. falciparum ookinetes, MLC-B (PF3D7_1118700) and MyoB both localize to the apical end but are expressed at completely different time points during development, indicating temporally uncoupled expression of the motor and its light chain.","method":"Immunofluorescence assay, gene deletion (genetic analysis)","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single localization method; no functional dissection specifically of MLC-B","pmids":["31283102"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"The MLC-B binding site resides within the lever arm region of PfMyoB (C-terminal 204 amino acids), as demonstrated by a conditional knock-out construct designed to excise this region including the lever arm containing the MLC-B light chain binding site; conditional excision of this region resulted in a truncated MyoB protein, confirming the structural requirement of this domain for MLC-B interaction.","method":"CRISPR-mediated conditional knock-out (DiCre/loxPint), genotyping PCR, live video microscopy","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic deletion defines the MLC-B binding region indirectly via domain excision, single lab, no direct biochemical confirmation of binding loss in this paper","pmids":["33104759"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MLC-B (PF3D7_1118700) is a MyoB-specific calmodulin-like light chain in Plasmodium falciparum that binds to the IQ2 motif within the lever arm of MyoB, co-localizes with MyoB at the extreme apical pole of invasive stages (merozoites, ookinetes, sporozoites), forms a stable complex with MyoB distinct from the glideosome, and is proposed to fulfill a tail-like structural/regulatory role for this tailless class XIV myosin."},"narrative":{"mechanistic_narrative":"MLC-B (PF3D7_1118700) is a MyoB-specific light chain in Plasmodium falciparum that acts as a dedicated calmodulin-like partner for the class XIV myosin MyoB rather than a component of the canonical glideosome [PMID:25802338]. It comprises a C-terminal calmodulin-like domain and an extended N-terminal region, co-localizes with MyoB at the extreme apical pole of merozoites, and forms a stable complex with MyoB by co-immunoprecipitation while failing to associate with glideosome proteins such as MTIP [PMID:25802338]. Biochemically, purified MLC-B binds the MyoB IQ2 motif in the lever-arm region in vitro [PMID:36273584], and the binding site maps to the C-terminal lever-arm region of MyoB [PMID:33104759], consistent with MLC-B serving a lever-arm-associated structural/regulatory role for this tailless myosin. In P. falciparum ookinetes, MLC-B and MyoB both localize apically but are expressed at distinct developmental time points, indicating their expression is temporally uncoupled [PMID:31283102]. Beyond these interaction and localization data, the specific motor-regulatory function of MLC-B has not been directly dissected in the available corpus.","teleology":[{"year":2015,"claim":"Establishing that MyoB has a dedicated light chain answered whether this tailless myosin uses a distinct regulatory partner separate from the glideosome machinery.","evidence":"Reciprocal co-immunoprecipitation, immunofluorescence, and domain analysis in P. falciparum with orthologs in P. berghei and P. knowlesi","pmids":["25802338"],"confidence":"Medium","gaps":["Whether the MLC-B–MyoB complex is required for invasion or motility was not tested","The functional role of the extended N-terminal region of MLC-B was not defined","No structural model of the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium knowlesi","strain":""}]},{"year":2019,"claim":"Comparing MLC-B and MyoB expression timing in ookinetes tested whether the light chain and its motor are co-regulated, revealing they are temporally uncoupled.","evidence":"Immunofluorescence and gene deletion analysis in P. falciparum ookinetes","pmids":["31283102"],"confidence":"Low","gaps":["Single localization method; no functional dissection specific to MLC-B","Consequence of temporal uncoupling for complex assembly not addressed","No live measurement of complex formation over the developmental timeline"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Localizing the MLC-B binding site to the MyoB lever arm addressed where on the motor the light chain docks and its structural requirement.","evidence":"CRISPR conditional knock-out (DiCre/loxPint) excising the C-terminal 204-aa lever-arm region of PfMyoB, with genotyping and live video microscopy","pmids":["33104759"],"confidence":"Low","gaps":["Binding loss inferred from domain excision, not directly confirmed biochemically in this study","Effect of losing MLC-B binding on MyoB function was not isolated from loss of the lever arm itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Reconstituting the interaction with purified proteins confirmed direct binding of MLC-B to the MyoB IQ2 motif and revealed that additional light chains can engage the same site.","evidence":"In vitro biochemical/biophysical binding assays with purified recombinant proteins and small-angle X-ray scattering in P. falciparum","pmids":["36273584"],"confidence":"Medium","gaps":["Whether MLC-B binding to IQ2 is preferential over the four other light chains in vivo is unresolved","No high-resolution structure of the MLC-B–IQ2 complex","Functional consequence of binding on MyoB motor activity not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct functional role of MLC-B in MyoB regulation, motility, or invasion remains undefined.","evidence":"No discovery in the corpus isolates an MLC-B-specific loss-of-function phenotype","pmids":[],"confidence":"Low","gaps":["No MLC-B-specific knockout/knockdown phenotype reported","No demonstration that MLC-B modulates MyoB motor activity","Role of the extended N-terminal region uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MyoB–MLC-B complex (distinct from the glideosome)"],"partners":["MYOB (MYOSIN B; VIA THE IQ2 MOTIF IN THE C-TERMINAL LEVER-ARM REGION)"],"other_free_text":["Contains a C-terminal calmodulin-like domain and an extended N-terminal region [#0]","Does not associate with glideosome proteins such as MTIP [#0]","MLC-B and MyoB are expressed at different developmental time points in P. falciparum ookinetes despite shared apical localization [#2]","Four other putative regulatory light chains also bind the MyoB IQ2 motif in vitro [#1]"]}},"prefetch_data":{},"corpus_meta":[{"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":["MLC-B"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36273584","id":"PMC_36273584","title":"Analysis of Plasmodium falciparum myosin B ATPase activity and structure in complex with the calmodulin-like domain of its light chain MLC-B.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/36273584","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MLC-B"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33104759","id":"","title":"Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33104759","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MLC-B"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31283102","id":"","title":"Systematic analysis of Plasmodium myosins reveals differential expression, localisation, and function in invasive and proliferative parasite stages.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31283102","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MLC-B"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27597808","id":"","title":"Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins.","date":"2016","source":"Evolutionary bioinformatics online","url":"https://pubmed.ncbi.nlm.nih.gov/27597808","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MLC-B"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6373,"output_tokens":1239,"usd":0.018852,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6049,"output_tokens":2291,"usd":0.04376,"stage2_stop_reason":"end_turn"},"total_usd":0.062612,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"MLC-B (PF3D7_1118700) was identified as a MyoB-specific light chain in P. falciparum; it contains a calmodulin-like domain at its C terminus and an extended N-terminal region, localizes to the extreme apical pole of merozoites co-incident with MyoB, and forms a complex with MyoB as shown by co-immunoprecipitation. MLC-B does not associate with glideosome complex proteins (e.g., MTIP).\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence localization, domain analysis across P. falciparum, P. berghei, and P. knowlesi\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and direct localization with functional interpretation, single lab, two orthogonal methods\",\n      \"pmids\": [\"25802338\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. falciparum, MLC-B (PF3D7_1118700) binds to the MyoB IQ2 motif in vitro, as established by biochemical/biophysical binding assays using purified recombinant proteins; additionally, four other putative regulatory light chains were found to bind the same MyoB IQ2 motif in vitro.\",\n      \"method\": \"Biochemical and biophysical binding assays (in vitro), small-angle X-ray scattering for low-resolution structure\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro reconstituted binding assay with purified recombinant proteins and biophysical characterization, single lab\",\n      \"pmids\": [\"36273584\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In P. falciparum ookinetes, MLC-B (PF3D7_1118700) and MyoB both localize to the apical end but are expressed at completely different time points during development, indicating temporally uncoupled expression of the motor and its light chain.\",\n      \"method\": \"Immunofluorescence assay, gene deletion (genetic analysis)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single localization method; no functional dissection specifically of MLC-B\",\n      \"pmids\": [\"31283102\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The MLC-B binding site resides within the lever arm region of PfMyoB (C-terminal 204 amino acids), as demonstrated by a conditional knock-out construct designed to excise this region including the lever arm containing the MLC-B light chain binding site; conditional excision of this region resulted in a truncated MyoB protein, confirming the structural requirement of this domain for MLC-B interaction.\",\n      \"method\": \"CRISPR-mediated conditional knock-out (DiCre/loxPint), genotyping PCR, live video microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic deletion defines the MLC-B binding region indirectly via domain excision, single lab, no direct biochemical confirmation of binding loss in this paper\",\n      \"pmids\": [\"33104759\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"MLC-B (PF3D7_1118700) is a MyoB-specific calmodulin-like light chain in Plasmodium falciparum that binds to the IQ2 motif within the lever arm of MyoB, co-localizes with MyoB at the extreme apical pole of invasive stages (merozoites, ookinetes, sporozoites), forms a stable complex with MyoB distinct from the glideosome, and is proposed to fulfill a tail-like structural/regulatory role for this tailless class XIV myosin.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MLC-B (PF3D7_1118700) is a MyoB-specific light chain in Plasmodium falciparum that acts as a dedicated calmodulin-like partner for the class XIV myosin MyoB rather than a component of the canonical glideosome [#0]. It comprises a C-terminal calmodulin-like domain and an extended N-terminal region, co-localizes with MyoB at the extreme apical pole of merozoites, and forms a stable complex with MyoB by co-immunoprecipitation while failing to associate with glideosome proteins such as MTIP [#0]. Biochemically, purified MLC-B binds the MyoB IQ2 motif in the lever-arm region in vitro [#1], and the binding site maps to the C-terminal lever-arm region of MyoB [#3], consistent with MLC-B serving a lever-arm-associated structural/regulatory role for this tailless myosin. In P. falciparum ookinetes, MLC-B and MyoB both localize apically but are expressed at distinct developmental time points, indicating their expression is temporally uncoupled [#2]. Beyond these interaction and localization data, the specific motor-regulatory function of MLC-B has not been directly dissected in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing that MyoB has a dedicated light chain answered whether this tailless myosin uses a distinct regulatory partner separate from the glideosome machinery.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, immunofluorescence, and domain analysis in P. falciparum with orthologs in P. berghei and P. knowlesi\",\n      \"pmids\": [\"25802338\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the MLC-B\\u2013MyoB complex is required for invasion or motility was not tested\",\n        \"The functional role of the extended N-terminal region of MLC-B was not defined\",\n        \"No structural model of the complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Comparing MLC-B and MyoB expression timing in ookinetes tested whether the light chain and its motor are co-regulated, revealing they are temporally uncoupled.\",\n      \"evidence\": \"Immunofluorescence and gene deletion analysis in P. falciparum ookinetes\",\n      \"pmids\": [\"31283102\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single localization method; no functional dissection specific to MLC-B\",\n        \"Consequence of temporal uncoupling for complex assembly not addressed\",\n        \"No live measurement of complex formation over the developmental timeline\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Localizing the MLC-B binding site to the MyoB lever arm addressed where on the motor the light chain docks and its structural requirement.\",\n      \"evidence\": \"CRISPR conditional knock-out (DiCre/loxPint) excising the C-terminal 204-aa lever-arm region of PfMyoB, with genotyping and live video microscopy\",\n      \"pmids\": [\"33104759\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Binding loss inferred from domain excision, not directly confirmed biochemically in this study\",\n        \"Effect of losing MLC-B binding on MyoB function was not isolated from loss of the lever arm itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Reconstituting the interaction with purified proteins confirmed direct binding of MLC-B to the MyoB IQ2 motif and revealed that additional light chains can engage the same site.\",\n      \"evidence\": \"In vitro biochemical/biophysical binding assays with purified recombinant proteins and small-angle X-ray scattering in P. falciparum\",\n      \"pmids\": [\"36273584\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MLC-B binding to IQ2 is preferential over the four other light chains in vivo is unresolved\",\n        \"No high-resolution structure of the MLC-B\\u2013IQ2 complex\",\n        \"Functional consequence of binding on MyoB motor activity not measured\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct functional role of MLC-B in MyoB regulation, motility, or invasion remains undefined.\",\n      \"evidence\": \"No discovery in the corpus isolates an MLC-B-specific loss-of-function phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No MLC-B-specific knockout/knockdown phenotype reported\",\n        \"No demonstration that MLC-B modulates MyoB motor activity\",\n        \"Role of the extended N-terminal region uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017022\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020007\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\n      \"MyoB\\u2013MLC-B complex (distinct from the glideosome)\"\n    ],\n    \"partners\": [\n      \"MyoB (myosin B; via the IQ2 motif in the C-terminal lever-arm region)\"\n    ],\n    \"other_free_text\": [\n      \"Contains a C-terminal calmodulin-like domain and an extended N-terminal region [#0]\",\n      \"Does not associate with glideosome proteins such as MTIP [#0]\",\n      \"MLC-B and MyoB are expressed at different developmental time points in P. falciparum ookinetes despite shared apical localization [#2]\",\n      \"Four other putative regulatory light chains also bind the MyoB IQ2 motif in vitro [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1118700","name":null,"product":"myosin light chain B","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0929400","name":null,"product":"myosin light chain B","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0916400","name":null,"product":"myosin light chain B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MLC-B","evaluation":null}