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

Edvards Liepinsh, M. Trexler, Andrei Kaikkonen, Johan Weigelt, L. Bányai, L. Patthy, Gottfried Otting

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5347-5353
Number of pages7
JournalEMBO Journal
Volume20
Issue number19
DOIs
Publication statusPublished - Oct 1 2001

Fingerprint

Deafness
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Mutation
Proteins
Cochlea
Disulfides
Pregnancy
Lung

Keywords

  • Deafness disorder
  • DFNA9
  • LCCL domain
  • NMR structure

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

NMR structure of the LCCL domain and implication for DFNA9 deafness disorder. / Liepinsh, Edvards; Trexler, M.; Kaikkonen, Andrei; Weigelt, Johan; Bányai, L.; Patthy, L.; Otting, Gottfried.

In: EMBO Journal, Vol. 20, No. 19, 01.10.2001, p. 5347-5353.

Research output: Contribution to journalArticle

Liepinsh, Edvards ; Trexler, M. ; Kaikkonen, Andrei ; Weigelt, Johan ; Bányai, L. ; Patthy, L. ; Otting, Gottfried. / NMR structure of the LCCL domain and implication for DFNA9 deafness disorder. In: EMBO Journal. 2001 ; Vol. 20, No. 19. pp. 5347-5353.
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