NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.
Related Articles NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.
EMBO J. 2001 Oct 1;20(19):5347-53
Authors: Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Bányai L, Patthy L, Otting G
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.
PMID: 11574466 [PubMed - indexed for MEDLINE]
Source:
PubMed