{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zheng L"],"funding":["National Institutes of Health"],"pagination":["E1452"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7602980"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(10)"],"pubmed_abstract":["The autosomal-dominant pleiotropic disorder called oculodentodigital dysplasia (ODDD) is caused by mutations in the gap junction protein Cx43. Of the 73 mutations identified to date, over one-third are localized in the cytoplasmic loop (Cx43CL) domain. Here, we determined the mechanism by which three ODDD mutations (M147T, R148Q, and T154A), all of which localize within the predicted 1-5-10 calmodulin-binding motif of the Cx43CL, manifest the disease. Nuclear magnetic resonance (NMR) and circular dichroism revealed that the three ODDD mutations had little-to-no effect on the ability of the Cx43CL to form α-helical structure as well as bind calmodulin. Combination of microscopy and a dye-transfer assay uncovered these mutations increased the intracellular level of Cx43 and those that traffi"],"journal":["Biomolecules"],"pubmed_title":["Calmodulin Directly Interacts with the Cx43 Carboxyl-Terminus and Cytoplasmic Loop Containing Three ODDD-Linked Mutants (M147T, R148Q, and T154A) that Retain α-Helical Structure, but Exhibit Loss-of-Function and Cellular Trafficking Defects."],"pmcid":["PMC7602980"],"funding_grant_id":["P30GM106397","GM072631","GM131092","S10RR027301"],"pubmed_authors":["Kieken F","Trease A","Chenavas S","Brownell S","Zheng L","Spagnol G","Anbanandam A","Sorgen PL"],"additional_accession":[]},"is_claimable":false,"name":"Calmodulin Directly Interacts with the Cx43 Carboxyl-Terminus and Cytoplasmic Loop Containing Three ODDD-Linked Mutants (M147T, R148Q, and T154A) that Retain α-Helical Structure, but Exhibit Loss-of-Function and Cellular Trafficking Defects.","description":"The autosomal-dominant pleiotropic disorder called oculodentodigital dysplasia (ODDD) is caused by mutations in the gap junction protein Cx43. Of the 73 mutations identified to date, over one-third are localized in the cytoplasmic loop (Cx43CL) domain. Here, we determined the mechanism by which three ODDD mutations (M147T, R148Q, and T154A), all of which localize within the predicted 1-5-10 calmodulin-binding motif of the Cx43CL, manifest the disease. Nuclear magnetic resonance (NMR) and circular dichroism revealed that the three ODDD mutations had little-to-no effect on the ability of the Cx43CL to form α-helical structure as well as bind calmodulin. Combination of microscopy and a dye-transfer assay uncovered these mutations increased the intracellular level of Cx43 and those that traffi","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2025-06-01T01:18:22.48Z","creation":"2020-11-08T09:53:07Z"},"accession":"S-EPMC7602980","cross_references":{"pubmed":["33080786"],"doi":["10.3390/biom10101452"]}}