{"id":"be5b7bda-82fb-5d80-a025-3e80957e96a4","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h4-activation","predicate":"activates_tested","statement":"Histamine-bound human H4 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4013a4e3-f664-542f-a5c7-92322c8678b3","mechanism_event_label":"The same histidine-derived messenger can activate a distinct receptor route.","subject":{"id":"847daefd-ce13-541a-b426-919975168a3d","slug":"histamine","display_name":"Histamine","entity_type_key":"small_molecule"},"object":{"id":"9fade788-dd37-57ea-b1aa-9ad6d6cc5e8f","slug":"hrh4","display_name":"Human histamine H4 receptor / HRH4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4013a4e3-f664-542f-a5c7-92322c8678b3","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h4-activation-event","event_type":"observed_relationship","label":"The same histidine-derived messenger can activate a distinct receptor route.","description":"Histamine-bound human H4 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"847daefd-ce13-541a-b426-919975168a3d","slug":"histamine","display_name":"Histamine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fade788-dd37-57ea-b1aa-9ad6d6cc5e8f","slug":"hrh4","display_name":"Human histamine H4 receptor / HRH4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"40ac3370-704c-5841-85af-ee7f534f9b32","slug":"human-hrh4-gi-coupling","display_name":"Human H4 receptor Gi coupling","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural stabilization, chimeric/mini G proteins and recombinant cells differ from native tissues; receptor engagement is not proof that oral histidine produces this response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The same histidine-derived messenger can activate a distinct receptor route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1be7b305-80c7-58d8-a7a2-4c1ca0c27b9b","evidence_kind":"source_excerpt","locator":"Lines 250-256","start_line":250,"end_line":256,"excerpt":"## histidine-h4-activation\nThe same histidine-derived messenger can activate a distinct receptor route.\nHistamine-bound human H4 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.\nModel: Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.\nLimitations: Structural stabilization, chimeric/mini G proteins and recombinant cells differ from native tissues; receptor engagement is not proof that oral histidine produces this response.\nEvidence access: Primary full text\nStructural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","model_system":"Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}