Amyloid fibril formation from a 9 amino acid peptide, 55th-63rd residues of human lysozyme.

Hen egg white lysozyme (HEWL) readily forms amyloid fibrils in vitro. We have previously identified a core structure, termed HEWL K-peptide, involved in fibril formation. Two major peptides, peptide #3 (50th-102nd residues of human lysozyme (hLZ)) and peptide #5 (54th-102nd residues), were isolated from the hLZ amyloid fibrils that had been exposed to pH 2.0 and 58 °C, and precipitated by ultra-centrifugation. These peptides cover most of the beta-domain and C-helix of hLZ including a 9 residues sequence corresponds to a human counterpart of HEWL K-peptide, GIFQINSRY (55th-63rd residues of hLZ, thus named "human K-peptide"). Chemically synthesized human K-peptide readily formed amyloid fibrils, as in HEWL K-peptide. It was demonstrated that both at least 9 residue length and Phe residue at 3rd position of the human K-peptide were crucial for amyloidogenesis in vitro. Short peptides covering COOH-terminal region of peptides #3 and #5 did not form amyloid fibrils. These data suggested that human K-peptide region with high propensity of amyloidogenesis plays a key role as a fibril-forming core sequence of hLZ. Interestingly, human K-peptide region is flanked by two predicted semi-disordered regions (39th-52nd and 67th-75th residues). We discuss the possible role of these regions.