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http://purl.uniprot.org/citations/21366346http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21366346http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21366346http://www.w3.org/2000/01/rdf-schema#comment"Neural cadherin (N-cadherin) is a calcium-dependent homophilic cell-adhesive molecule and critical for synaptogenesis and synapse maintenance. The extracellular region plays an important role in cadherin-mediated cell adhesion and has five tandemly repeated ectodomains (EC1-EC5) with three calcium-binding sites situated between each of these domains. Adhesive dimer formation is significantly dependent on binding of calcium such that mutations in the calcium-binding sites adversely affect cell adhesion. To investigate the relative significance of the calcium-binding sites at the EC1-EC2 interface in calcium-induced dimerization, we mutated three important amino acids, D134, D136, and D103, in NCAD12, a construct containing EC1 and EC2. Spectroscopic and chromatographic experiments showed that all three mutations affected calcium binding and dimerization. Mutation of D134, a bidentate chelator in site 3, severely impaired the binding of calcium to all three sites. These findings confirm that binding to site 3 is required for binding to occur at site 2 and site 1. Interestingly, while the D103A mutation diminished only the affinity for calcium, it completely eliminated dimerization. Equilibrium dialysis experiments showed a stoichiometry of 3 at 2 mM calcium for D103A, but no dimerization was apparent even at 10 mM calcium. These results indicate that calcium binding alone is not sufficient for dimerization but requires cooperativity between calcium-binding sites. In summary, our findings confirm that the calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1, and that cooperativity between site 2 and site 1 is essential for formation of adhesive dimers by N-cadherin."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.org/dc/terms/identifier"doi:10.1021/bi101872b"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.org/dc/terms/identifier"doi:10.1021/bi101872b"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/author"Pedigo S."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/author"Pedigo S."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/author"Vunnam N."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/author"Vunnam N."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/name"Biochemistry"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/name"Biochemistry"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/pages"2973-2982"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/pages"2973-2982"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/title"Sequential binding of calcium leads to dimerization in neural cadherin."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/title"Sequential binding of calcium leads to dimerization in neural cadherin."xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/volume"50"xsd:string
http://purl.uniprot.org/citations/21366346http://purl.uniprot.org/core/volume"50"xsd:string
http://purl.uniprot.org/citations/21366346http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21366346
http://purl.uniprot.org/citations/21366346http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21366346
http://purl.uniprot.org/citations/21366346http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21366346
http://purl.uniprot.org/citations/21366346http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21366346
http://purl.uniprot.org/uniprot/P15116http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/21366346
http://purl.uniprot.org/uniprot/P15116#attribution-D7A1E78E885FD3DE1279C7459607759Ehttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/21366346