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Identification of an amyloidogenic region on keratoepithelin via synthetic peptides
Author(s) -
Yuan Ching,
Berscheit Heather L.,
Huang Andrew J.W.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.12.019
Subject(s) - thioflavin , fibril , amyloid (mycology) , congo red , chemistry , peptide , circular dichroism , amyloidosis , amyloid disease , biochemistry , in vitro , microbiology and biotechnology , biophysics , amyloid fibril , biology , pathology , amyloid β , alzheimer's disease , medicine , inorganic chemistry , disease , organic chemistry , adsorption
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.