{"id":"e69c24a2-e012-54b0-a8fe-f70cf0acdd4e","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-mct8-t3-recognition","predicate":"binds","statement":"Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c6a0cf78-aa60-5f5b-bd6f-8ffe5618cd81","mechanism_event_label":"The transporter recognizes the shape and chemical groups of iodine-containing T3.","subject":{"id":"98c25617-10b5-50ab-b330-7e6b7fa595bb","slug":"slc16a2","display_name":"Human MCT8 / SLC16A2","entity_type_key":"protein"},"object":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"c6a0cf78-aa60-5f5b-bd6f-8ffe5618cd81","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-mct8-t3-recognition-event","event_type":"biochemical_relationship","label":"The transporter recognizes the shape and chemical groups of iodine-containing T3.","description":"Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"98c25617-10b5-50ab-b330-7e6b7fa595bb","slug":"slc16a2","display_name":"Human MCT8 / SLC16A2","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"role":"ligand","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"393d2192-4809-54d7-a96d-c8a61bca9d4b","slug":"crym","display_name":"mu-Crystallin / CRYM","entity_type_key":"protein"},"role":"intracellular_hormone_retention_factor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_locator","value_text":"Results: T3 recognition, Figure 3; Methods","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/40140416.txt\", \"locator\": \"Results: T3 recognition, Figure 3; Methods\", \"start_char\": 679, \"end_char\": 2779}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical.","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":"The transporter recognizes the shape and chemical groups of iodine-containing T3.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HeLa cells for transport; HEK293F cells for protein production","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2040b817-6329-5518-90a4-cea79e57fe27","evidence_kind":"source_excerpt","locator":"Lines 912-924","start_line":912,"end_line":924,"excerpt":"### i-met-mct8-t3-recognition\nHuman MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The transporter recognizes the shape and chemical groups of iodine-containing T3.\norganism: Human\ntissue_or_cell_type: HeLa cells for transport; HEK293F cells for protein production\nexperimental_model: Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis\nlimitations: Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical.\nexposure: Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C.\nevidence_locator: Results: T3 recognition, Figure 3; Methods\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/40140416.txt\", \"locator\": \"Results: T3 recognition, Figure 3; Methods\", \"start_char\": 679, \"end_char\": 2779}]\n[i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8","model_system":"Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8","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}