title: Structural models of amyloid-like fibrils.
abstract: Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble proteins. Both of these groups of fibrils, despite differences in the sequence and native structure of their component proteins, share common properties, including their core structure. Multiple models have been proposed for the common core structure, but in most cases, atomic-level structural details have yet to be determined. Here we review several structural models proposed for amyloid and amyloid-like fibrils and relate features of these models to the common fibril properties. We divide models into three classes: Refolding, Gain-of-Interaction, and Natively Disordered. The Refolding models propose structurally distinct native and fibrillar states and suggest that backbone interactions drive fibril formation. In contrast, the Gain-of-Interaction models propose a largely native-like structure for the protein in the fibril and highlight the importance of specific sequences in fibril formation. The Natively Disordered models have aspects in common with both Refolding and Gain-of-Interaction models. While each class of model suggests explanations for some of the common fibril properties, and some models, such as Gain-of-Interaction models with a cross-beta spine, fit a wider range of properties than others, no one class provides a complete explanation for all amyloid fibril behavior.
authors.affiliation: Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, California 90095, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nelson
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000682:Amyloid