{"id":"1153833d-05e8-51ce-b953-5f13bebe2ab8","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-cb2-gi-structure","predicate":"forms_complex_with","statement":"The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cf1a93f2-0ac6-5620-baee-929fa6fc8dda","mechanism_event_label":"The receptor was caught in the act of holding its signalling partner.","subject":{"id":"5abfafd4-17c3-587a-8f02-e38cce8f8028","slug":"cnr2","display_name":"Human cannabinoid receptor 2 / CB2 / CNR2","entity_type_key":"protein"},"object":{"id":"0b076d4a-43cc-53c6-ade5-7697be49894e","slug":"gi-o-proteins","display_name":"Heterotrimeric Gi/o proteins","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"cf1a93f2-0ac6-5620-baee-929fa6fc8dda","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-cb2-gi-structure-event","event_type":"biochemical_relationship","label":"The receptor was caught in the act of holding its signalling partner.","description":"The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ea289a29-05f8-5bcb-9100-1cc876b25068","slug":"cb2-gi-complex","display_name":"The CB2 receptor in complex with heterotrimeric Gi","entity_type_key":"protein_complex"},"role":"resolved_complex","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5abfafd4-17c3-587a-8f02-e38cce8f8028","slug":"cnr2","display_name":"Human cannabinoid receptor 2 / CB2 / CNR2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0b076d4a-43cc-53c6-ade5-7697be49894e","slug":"gi-o-proteins","display_name":"Heterotrimeric Gi/o proteins","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/thc-research/32004460.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92\", \"start_char\": 0, \"end_char\": 885, \"text_sha256\": \"928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Agonist-bound receptor coupled to Gi","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.","comparator":null,"unit":null,"notes":"","entity":{"slug":"tetrahydrocannabinol","display_name":"Delta-9-tetrahydrocannabinol / THC","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human receptor complex","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The receptor was caught in the act of holding its signalling partner.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. (2020). https://pubmed.ncbi.nlm.nih.gov/32004460/ DOI: 10.1016/j.cell.2020.01.007","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified signalling complex","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"de0efe27-bd37-519c-a02c-c073e9a5ff14","evidence_kind":"source_excerpt","locator":"Lines 140-151","start_line":140,"end_line":151,"excerpt":"### thc-cb2-gi-structure\nThe cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.\nCondition category: normal\nnutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.\nplain_language: The receptor was caught in the act of holding its signalling partner.\norganism: Human receptor complex\ntissue_or_cell_type: Purified signalling complex\nexperimental_model: Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi\nlimitations: Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred.\nexposure: Agonist-bound receptor coupled to Gi\nevidence_span: {\"source_cache\": \"artifacts/thc-research/32004460.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92\", \"start_char\": 0, \"end_char\": 885, \"text_sha256\": \"928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92\"}\n[thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. 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