Within the past 10 years, several groups have demonstrated that proteins not associated with disease also can form amyloid. These studies suggest that while all proteins have the potential to aggregate, evolutionary pressure causes them to avoid unproductive folding pathways [2]. Since its discovery in 1922, lysozyme and its homologs have served as model
JTP-74057 for the study of protein folding, structure, and function [3]. The native lysozymes are highly soluble, monomeric, stable globular proteins. Hen egg white lysozyme (HEWL), one of the most commonly studied lysozymes, has been shown to form amyloid fibrils under a variety of conditions that promote partial unfolding and/or fragmentation [4], [5] and [6]. Addition of denaturants has also been shown to induce fibril formation when concentrations promote partial unfolding rather than complete denaturation [7]. Data from studies of lysozyme and a variety of other
proteins under aqueous conditions demonstrate a correlation between aggregation and physicochemical properties such as charge, hydrophobicity, and secondary structure propensity [8].
