An alanine to proline mutation in the 1A rod domain of the keratin 10 chain in epidermolytic hyperkeratosis

J Invest Dermatol. 1997 Nov;109(5):692-4. doi: 10.1111/1523-1747.ep12338320.

Abstract

We report a mutation in a case of epidermolytic hyperkeratosis that results in a proline for alanine substitution in the residue position 12 of the 1A subdomain of the keratin 10 chain (codon 158). The disease phenotype is consistent with the inappropriate substitution of a proline near the beginning of the rod domain, because it is likely to seriously disrupt the structural organization of coiled-coil molecules within keratin intermediate filaments. Mutations/substitutions in this position have not been reported in any keratin disease. Position 12 is an alanine in all intermediate filament chains, and lies in the outer b heptad position of the coiled-coil. In vitro peptide interference assembly assays revealed that substitutions that alter residue size or charge at this position primarily interfere with keratin filament elongation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alanine / genetics*
  • Female
  • Humans
  • Hyperkeratosis, Epidermolytic / genetics*
  • Intermediate Filaments / chemistry
  • Keratins / chemistry*
  • Keratins / genetics
  • Male
  • Pedigree
  • Point Mutation*
  • Proline / genetics*
  • Protein Structure, Tertiary

Substances

  • Keratins
  • Proline
  • Alanine