Creation of amyloid fibrils from mutant Asn187 gelsolin peptides

Biochem Biophys Res Commun. 1992 Feb 28;183(1):227-31. doi: 10.1016/0006-291x(92)91632-z.

Abstract

The amyloid protein in familial amyloidosis, Finnish type, is a 71 amino acid long fragment of the inner region of mutant Asp187----Asn gelsolin. The mechanism of gelsolin amyloid formation was tested with synthetic 11 and 30 residue peptides corresponding to the normal and mutant sequence of gelsolin. Fibrils meeting the morphologic criteria of amyloid were formed from the mutant Asn187 peptides. Substitution of the normal Asp187 residue with the mutant Asn residue resulted in a 9-fold increase in fibrillogenicity as determined by quantitative fluorometry. The present study demonstrates the first successful in vitro creation of amyloid-like fibrils from Asn187 gelsolin peptides and provides evidence that amyloid formation in Finnish amyloidosis is a direct consequence of the Asp187----Asn substitution in gelsolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / genetics
  • Amyloid / metabolism*
  • Amyloidosis / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Gelsolin
  • Humans
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*

Substances

  • Amyloid
  • Calcium-Binding Proteins
  • Gelsolin
  • Microfilament Proteins
  • Peptide Fragments