| http://purl.uniprot.org/citations/21216247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21216247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21216247 | http://www.w3.org/2000/01/rdf-schema#comment | "Otoferlin (Otof), whose genetic mutations cause profound deafness in humans, is a protein composed of at least six C(2) domains, which are known as Ca(2)(+)-binding and phospholipid-binding regions. Mammalian ferlin proteins are proposed to act in membrane fusion events, with Otof being specifically required for exocytosis in auditory hair cells. Ferlin C(2) domains exhibit a rather low level of sequence similarity to those of synaptotagmins, protein kinase C isoforms, or phospholipases. Here, we report the crystal structure of the N-terminal C(2) domain of Otof (C₂A) at 1.95-Å resolution. In contrast to previous predictions, we found that this C(2) domain is complete with eight β-strands. Comparing the structure of Otof C₂A to those of other C(2) domains revealed one top loop in Otof to be significantly shorter. This results in a depression of the surface, which is positively charged for the Otof C₂A domain, and contrasts with the head-like protrusion surrounded by a negatively charged "neck" typically found in other C(2) domains. Isothermal titration calorimetry and circular dichroism spectroscopy studies confirmed that Otof C₂A is unable to bind Ca(2+), while the synaptotagmin-1 C₂A domain exhibited Ca(2+) binding under the same conditions. Furthermore, floatation assays revealed a failure of Otof C(2)A to bind to phospholipid membranes. Accordingly, no positively charged β-groove-like surface structure, which is known to bind phosphatidylinositol-4,5-bisphosphate in other C(2) domains, was found at the respective position in Otof C₂A. Taken together, these data demonstrate that the Otof C₂A domain differs structurally and functionally from other C(2) domains."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2010.12.031"xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2010.12.031"xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Ficner R."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Ficner R."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Neumann P."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Neumann P."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Tittmann K."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Tittmann K."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Helfmann S."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Helfmann S."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Moser T."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Moser T."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Reisinger E."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/author | "Reisinger E."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/pages | "479-490"xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/pages | "479-490"xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/title | "The crystal structure of the CA domain of otoferlin reveals an unconventional top loop region."xsd:string |
| http://purl.uniprot.org/citations/21216247 | http://purl.uniprot.org/core/title | "The crystal structure of the CA domain of otoferlin reveals an unconventional top loop region."xsd:string |