Identification of an amyloidogenic region on keratoepithelin via synthetic peptides

Ching Yuan, Heather L. Berscheit, Andrew J W Huang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Mutations of keratoepithelin (KE) gene in human chromosome 5q31 have been linked with corneal epithelial or stromal dystrophies characterized by the abnormal deposits of amyloid fibrils and/or non-amyloid aggregations in corneal tissue. We report herein that synthetic peptide containing amino acid (a.a.) residues of 515-532 of native KE protein can readily form β-sheet-containing amyloid fibrils in vitro. Amyloid fibrils formed in various conditions from short synthetic peptides (containing a.a. 515-532 and 515-525, respectively) were characterized by thioflavin T (ThT) fluorescence assay, Congo red staining, electron microscopy (EM) and circular dichroism (CD). Triple-N-methylation of the synthetic peptides prevented the β-sheet polymerization and related amyloid fibril formation. Comparison study with ThT fluorescence further demonstrated that synthetic peptides containing corneal dystrophy-related mutations within this region formed amyloid fibrils to various extents. Our results suggest that each individual dystrophy-related mutation by itself does not necessarily potentiate amyloid fibril formation of KE. Roles of these intrinsically amyloidogenic foci in abnormal KE aggregations and amyloid deposits of stromal corneal dystrophies await further investigation.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalFEBS Letters
Volume581
Issue number2
DOIs
StatePublished - Jan 23 2007

Bibliographical note

Funding Information:
This work was supported in part by grants from Fight-for-Sight, Minnesota Medical Foundation, Eye Bank Association of America and Research to Prevent Blindness.

Keywords

  • Amyloid fibrils
  • Amyloidogenesis
  • Corneal dystrophies
  • Keratoepithelin
  • Synthetic peptide
  • Transforming growth factor beta 1

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