Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO J. 2001 Oct 1;20(19):5347-53.

NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.

Author information

  • 1Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.

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.

PMID:
11574466
[PubMed - indexed for MEDLINE]
PMCID:
PMC125649
Free PMC Article

Images from this publication.See all images (3)Free text

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk