{"id":"a7e4f57a-d115-5d32-9865-5a369cfb3fd7","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-t3-thrb-ligand-binding","predicate":"binds","statement":"T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0a696852-3289-5921-8294-b1abc65e4531","mechanism_event_label":"T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.","subject":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"object":{"id":"1c205be4-c767-55e3-9eea-78086a4c1df3","slug":"human-thrb-lbd-202-461","display_name":"Human THRB ligand-binding domain 202–461","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"0a696852-3289-5921-8294-b1abc65e4531","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-t3-thrb-ligand-binding-event","event_type":"biochemical_relationship","label":"T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.","description":"T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"role":"bound_ligand","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1c205be4-c767-55e3-9eea-78086a4c1df3","slug":"human-thrb-lbd-202-461","display_name":"Human THRB ligand-binding domain 202–461","entity_type_key":"protein_state"},"role":"receptor_construct","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"012e6f8c-edb7-5962-bdc9-a075c7742137","slug":"thrb","display_name":"Thyroid hormone receptor beta","entity_type_key":"protein"},"role":"parent_protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6a104a24-52ab-54ca-a596-a6cf642a98a5","slug":"human-rxra-lbd-223-462","display_name":"Human RXRA ligand-binding domain 223–462","entity_type_key":"protein_state"},"role":"heterodimer_partner_construct","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7dc1ce11-f208-5187-95d9-96b07927df6a","slug":"rxra","display_name":"Retinoid X receptor alpha","entity_type_key":"protein"},"role":"parent_partner_protein","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5e5ba4c8-332e-553e-bd31-c6ce422bc398","slug":"src2-hkilhrll-peptide","display_name":"SRC-2-derived HKILHRLL coactivator peptide","entity_type_key":"protein_state"},"role":"bound_coactivator_peptide","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"96fe9a12-b921-5454-9ee8-7e21891d91d0","slug":"ncoa2","display_name":"Nuclear receptor coactivator 2 / TIF2","entity_type_key":"protein"},"role":"parent_coactivator","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Figure 2a and Results: structural characterization; Methods: protein production and crystallography","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/26289479.txt\", \"locator\": \"Figure 2a and Results: structural characterization; Methods: protein production and crystallography\", \"start_char\": 10702, \"end_char\": 12152}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human receptor domains produced in Escherichia coli; synthetic coactivator peptide","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified receptor-domain complex","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bd64eca3-13bf-5417-acf6-83177597306e","evidence_kind":"source_excerpt","locator":"Lines 1172-1185","start_line":1172,"end_line":1185,"excerpt":"### i-met-t3-thrb-ligand-binding\nT3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.\norganism: Human receptor domains produced in Escherichia coli; synthetic coactivator peptide\ntissue_or_cell_type: Purified receptor-domain complex\nexperimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays\nlimitations: Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold.\nexposure: Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution.\ncross_nutrient: An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation.\nevidence_locator: Figure 2a and Results: structural characterization; Methods: protein production and crystallography\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/26289479.txt\", \"locator\": \"Figure 2a and Results: structural characterization; Methods: protein production and crystallography\", \"start_char\": 10702, \"end_char\": 12152}]\n[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. 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