NMR structure of the LCCL domain
[COCH_HUMAN] Defects in COCH are the cause of deafness autosomal dominant type 9 (DFNA9) [MIM:601369]. DFNA9 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA9 is characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Deafness is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers.     
Publication Abstract from PubMed
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.
NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.,Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Banyai L, Patthy L, Otting G EMBO J. 2001 Oct 1;20(19):5347-53. PMID:11574466
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.