Unzipping the mysteries of amyloid fiber formation
- Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520-8114
Interest in the phenomenon of protein aggregation is as old as protein research. For example, changes in activity and covalent structure accompanying “coagulum” formation by insulin were important to the elucidation of the molecular origins of hormone action (1). In recent memory, the phenomenon of aggregation served only as an annoyance to the research biochemist and a serious economic consideration in the production and distribution of protein pharmaceuticals. Now, however, one class of aggregate has drawn considerable interest from a range of disciplines. These aggregates are readily identified ultrastructurally by the presence of nonamorphous, filamentous structures, termed amyloid fibers.
Function and Pathology
Two diverse groups share an interest in these systems. The first are those interested in the biological and biomedical relevance. Amyloid fibers are involved in a range of human conditions, e.g., Alzheimer's disease and type II diabetes (2, 3). The conversion of a normally soluble protein into amyloid can give rise to a gain in toxic function or a loss of function, or can result in occlusion of normal cellular or organ function. Furthermore, there is growing evidence that amyloid can be used productively by organisms (4). For example, in Escherichia coli, the deposition of the protein curli as amyloid serves as a substrate for colony and biofilm formation (5). In humans, it has recently been suggested that similar conversions in conformation of cytoplasmic polyadenylation element-binding proteins are central to the maintenance of long-term memory (6). The second group are those interested in the development of novel materials (7, 8). Amyloid fibers template their own assembly, giving rise to reproducible structures on the nanometer scale. The precursors are readily synthesized or are biologically expressed, allowing for a range of derivitization. The reaction conditions for assembly can be environmentally friendly and yet yield fibers that are physically and chemically …
