{"id":"17b1282e-dbb8-5b0f-809e-476ef9c06f86","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:galpha-r209c-removes-magnesium-dependence","predicate":"reduces-magnesium-dependence-of","statement":"The low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"2881814a-3908-5847-a3d3-d1963462f090","mechanism_event_label":"The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind.","subject":{"id":"8c019225-5dec-5160-ac90-50237ff24106","slug":"gnai1-r209c","display_name":"GNAI1 R209C experimental mutant","entity_type_key":"protein_state"},"object":{"id":"9c9409b9-1a55-5d15-afdb-52314c9082a7","slug":"g-alpha-nucleotide-exchange","display_name":"G protein alpha guanine-nucleotide exchange","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2881814a-3908-5847-a3d3-d1963462f090","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:galpha-r209c-removes-magnesium-dependence-event","event_type":"biochemical_relationship","label":"The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind.","description":"The low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c8ee3465-3054-5b36-ba07-79cb46bd8ec9","slug":"gnai1","display_name":"G protein alpha-i1 subunit / GNAI1","entity_type_key":"protein"},"role":"wild-type comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"role":"receptor comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"sensitivity variable","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bf7dccfe-8518-5e49-aa95-5cface204ec1","slug":"gtp-gamma-s","display_name":"Guanosine 5-prime-O-(3-thiotriphosphate)","entity_type_key":"small_molecule"},"role":"assay ligand","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"8c019225-5dec-5160-ac90-50237ff24106","slug":"gnai1-r209c","display_name":"GNAI1 R209C experimental mutant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9c9409b9-1a55-5d15-afdb-52314c9082a7","slug":"g-alpha-nucleotide-exchange","display_name":"G protein alpha guanine-nucleotide exchange","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"magnesium -> CaSR/PTH -> calcium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Engineered receptor and Galpha comparison in reconstituted signaling assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered mutant evidence is separate from nutrient deficiency; no claim that R209C occurs in affected patients or that every receptor mechanism is excluded.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human CaSR expression system; engineered G-protein preparation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK-293 membrane reconstitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"9aa3c2af-22bd-55d2-a2e0-cefdaab9fa09","evidence_kind":"source_excerpt","locator":"Lines 469-479","start_line":469,"end_line":479,"excerpt":"### galpha-r209c-removes-magnesium-dependence\nThe low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it.\nCondition category: machinery_impairment\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind.\norganism: Human CaSR expression system; engineered G-protein preparation\ntissue_or_cell_type: HEK-293 membrane reconstitution\nexperimental_model: Engineered receptor and Galpha comparison in reconstituted signaling assays\nlimitations: Engineered mutant evidence is separate from nutrient deficiency; no claim that R209C occurs in affected patients or that every receptor mechanism is excluded.\ncross_nutrient: magnesium -> CaSR/PTH -> calcium\n[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200","model_system":"Engineered receptor and Galpha comparison in reconstituted signaling assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (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":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}