Normal and aberrant biological self-assembly: insights from studies of human lysozyme and its amyloidogenic variants

Studies of lysozyme have played a major role over several decades in defining the general principles underlying protein structure, folding, and stability. Following the discovery some 10 years ago that two mutational variants of lysozyme are associated with systemic amyloidosis, these studies have been extended to inves-tigate the mechanism of amyloid fibril formation. This Account describes our present knowledge of lysozyme folding and misfold-ing, and how the latter can give rise to amyloid disease. It also discusses the significance of these studies for our general under-standing of normal and aberrant protein folding in the context of human health and disease. 1