Identification of an amyloidogenic region on keratoepithelin via synthetic peptides.

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