{"id":"ed889997-fddb-5ca7-a893-85126f4950f9","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:calcium-rigidifies-e-cadherin","predicate":"stabilizes","statement":"Three Ca2+ ions coordinated at the interface of mouse E-cadherin extracellular domains 1 and 2 support their extended, rigid arrangement.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e1e37745-efbf-53c4-aa44-9914835aaa7f","mechanism_event_label":"Calcium braces the outside portion of a cell-adhesion protein.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"object":{"id":"8dc302c2-44c1-59fe-9083-967f6b76370f","slug":"cdh1-ectodomain-rigidity","display_name":"E-cadherin ectodomain rigidity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e1e37745-efbf-53c4-aa44-9914835aaa7f","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:calcium-rigidifies-e-cadherin-event","event_type":"biochemical_relationship","label":"Calcium braces the outside portion of a cell-adhesion protein.","description":"Three Ca2+ ions coordinated at the interface of mouse E-cadherin extracellular domains 1 and 2 support their extended, rigid arrangement.","status":"provisional","compartment":{"slug":"extracellular-space","display_name":"Extracellular space"},"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"interdomain_structural_ligand","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d0c1132c-c4fd-557d-bc53-11c3ea1ff7ae","slug":"cdh1","display_name":"E-cadherin / CDH1","entity_type_key":"protein"},"role":"adhesion_protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8dc302c2-44c1-59fe-9083-967f6b76370f","slug":"cdh1-ectodomain-rigidity","display_name":"E-cadherin ectodomain rigidity","entity_type_key":"cellular_process"},"role":"structural_outcome","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3dcbbcaa-17df-54a0-a499-9b966a38631a","slug":"extracellular-space","display_name":"Extracellular space","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":3,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"compartment_description","value_text":"Extracellular domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two-domain crystal structure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The crystallized fragment is not a complete living adherens junction; crystal dimer geometry alone does not define every adhesion contact.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Calcium braces the outside portion of a cell-adhesion protein.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nagar1996] Structural basis of calcium-induced E-cadherin rigidification and dimerization (1996). https://pubmed.ncbi.nlm.nih.gov/8598933/ DOI: 10.1038/380360a0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified E-cadherin ectodomain","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e1aadadd-0544-59a8-b281-f07790ba102f","evidence_kind":"source_excerpt","locator":"Lines 1128-1138","start_line":1128,"end_line":1138,"excerpt":"### calcium-rigidifies-e-cadherin\nThree Ca2+ ions coordinated at the interface of mouse E-cadherin extracellular domains 1 and 2 support their extended, rigid arrangement.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Calcium braces the outside portion of a cell-adhesion protein.\norganism: Mus musculus protein\ntissue_or_cell_type: Purified E-cadherin ectodomain\nexperimental_model: Two-domain crystal structure\nlimitations: The crystallized fragment is not a complete living adherens junction; crystal dimer geometry alone does not define every adhesion contact.\ncompartment_description: Extracellular domain\n[nagar1996] Structural basis of calcium-induced E-cadherin rigidification and dimerization (1996). https://pubmed.ncbi.nlm.nih.gov/8598933/ DOI: 10.1038/380360a0","model_system":"Two-domain crystal structure","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [nagar1996] Structural basis of calcium-induced E-cadherin rigidification and dimerization (1996). https://pubmed.ncbi.nlm.nih.gov/8598933/ DOI: 10.1038/380360a0","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (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":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"2b879c92-ff91-5aa9-a2af-00bbdbf92d01","title":"Calcium-stabilized E-cadherin structure does not guarantee soluble self-association","kind":"context_difference","status":"open","why":"A two-domain crystal displayed dimer contacts, whereas the isolated full ectodomain did not self-associate in the solution study. Research comparison category: construct_and_assay_difference.","resolution":"Curation interpretation: retain calcium-dependent rigidity and protease protection, while avoiding a claim that calcium alone creates a complete adhesive junction.","created_at":"2026-09-17 08:08:54","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/2b879c92-ff91-5aa9-a2af-00bbdbf92d01","sides":[{"conflict_id":"2b879c92-ff91-5aa9-a2af-00bbdbf92d01","ordinal":0,"label":"Calcium braces the outside portion of a cell-adhesion protein.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":1128,"end_line":1138,"quote":"### calcium-rigidifies-e-cadherin\nThree Ca2+ ions coordinated at the interface of mouse E-cadherin extracellular domains 1 and 2 support their extended, rigid arrangement.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Calcium braces the outside portion of a cell-adhesion protein.\norganism: Mus musculus protein\ntissue_or_cell_type: Purified E-cadherin ectodomain\nexperimental_model: Two-domain crystal structure\nlimitations: The crystallized fragment is not a complete living adherens junction; crystal dimer geometry alone does not define every adhesion contact.\ncompartment_description: Extracellular domain\n[nagar1996] Structural basis of calcium-induced E-cadherin rigidification and dimerization (1996). https://pubmed.ncbi.nlm.nih.gov/8598933/ DOI: 10.1038/380360a0","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["ed889997-fddb-5ca7-a893-85126f4950f9"]},{"conflict_id":"2b879c92-ff91-5aa9-a2af-00bbdbf92d01","ordinal":1,"label":"Bound calcium helps keep the adhesion protein folded and resistant to protease attack.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":1140,"end_line":1150,"quote":"### calcium-protects-e-cadherin-from-proteolysis\nCalcium binding protected the recombinant mouse E-cadherin ectodomain from tryptic cleavage; calcium depletion caused a reversible conformational change.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Bound calcium helps keep the adhesion protein folded and resistant to protease attack.\norganism: Mus musculus protein expressed in insect cells\ntissue_or_cell_type: Purified extracellular domain\nexperimental_model: Calcium titration, electron microscopy and trypsin assay\nlimitations: In-vitro calcium removal is not dietary calcium deficiency; the soluble fragment did not self-associate under these assay conditions.\ncompartment_description: Extracellular domain\n[pokutta1994] Conformational changes of the recombinant extracellular domain of E-cadherin upon calcium binding (1994). https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1994.tb19080.x DOI: 10.1111/j.1432-1033.1994.tb19080.x","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["43be7d23-03e0-5196-b32f-9802886c24b9"]}]}],"corrections":[],"research":null}