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- Title
NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.
- Authors
Liepinsh, E; Trexler, M; Kaikkonen, A; Weigelt, J; Bányai, L; Patthy, L; Otting, G
- Abstract
The LCCL domain is a recently discovered, conserved protein module named after its presence in Limulus factor C, cochlear protein Coch-5b2 and late gestation lung protein Lgl1. The LCCL domain plays a key role in the autosomal dominant human deafness disorder DFNA9. Here we report the nuclear magnetic resonance (NMR) structure of the LCCL domain from human Coch-5b2, where dominant mutations leading to DFNA9 deafness disorder have been identified. The fold is novel. Four of the five known DFNA9 mutations are shown to involve at least partially solvent-exposed residues. Except for the Trp91Arg mutant, expression of these four LCCL mutants resulted in misfolded proteins. These results suggest that Trp91 participates in the interaction with a binding partner. The unexpected sensitivity of the fold with respect to mutations of solvent-accessible residues might be attributed to interference with the folding pathway of this disulfide-containing domain.
- Publication
The EMBO journal, 2001, Vol 20, Issue 19, p5347
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/20.19.5347