{"id":"826bd1a4-47bb-5b40-ae9e-89b8e0ab7494","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-oatp1c1-t4-binding","predicate":"binds","statement":"The 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"fc8f0698-6685-5a7c-88df-bac3a6baf158","mechanism_event_label":"OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4.","subject":{"id":"9b5cfed2-35db-55db-87ce-9f43c4c8ce33","slug":"slco1c1","display_name":"Human OATP1C1 / SLCO1C1","entity_type_key":"protein"},"object":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"fc8f0698-6685-5a7c-88df-bac3a6baf158","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-oatp1c1-t4-binding-event","event_type":"biochemical_relationship","label":"OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4.","description":"The 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9b5cfed2-35db-55db-87ce-9f43c4c8ce33","slug":"slco1c1","display_name":"Human OATP1C1 / SLCO1C1","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"bound_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_locator","value_text":"Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/40680733.txt\", \"locator\": \"Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3\", \"start_char\": 30218, \"end_char\": 32418}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"T4-bound cryo-EM structure; complementary radiolabeled-T4 uptake experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Static structure; possible lateral entry and lipid cotransport are not established by this record.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified human membrane transporter","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1c43ad46-1532-5b43-89e2-0da4b77ba3d8","evidence_kind":"source_excerpt","locator":"Lines 954-966","start_line":954,"end_line":966,"excerpt":"### i-met-oatp1c1-t4-binding\nThe 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4.\norganism: Human\ntissue_or_cell_type: Purified human membrane transporter\nexperimental_model: Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays\nlimitations: Static structure; possible lateral entry and lipid cotransport are not established by this record.\nexposure: T4-bound cryo-EM structure; complementary radiolabeled-T4 uptake experiments.\nevidence_locator: Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/40680733.txt\", \"locator\": \"Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3\", \"start_char\": 30218, \"end_char\": 32418}]\n[i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032","model_system":"Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}