NMR structure of the LCCL domain and implication for DFNA9 deafness disorder

Edvards Liepinsh, Mária Trexler, Andrei Kaikkonen, Johan Weigelt, László Bányai, László Patthy, Gottfried Otting

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45 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5347-5353
Number of pages7
JournalEMBO Journal
Issue number19
Publication statusPublished - Oct 1 2001



  • DFNA9
  • Deafness disorder
  • LCCL domain
  • NMR structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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