title: The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation.
abstract: Amyloid fibrils and prions are proteinaceous aggregates that are based on a unique form of polypeptide configuration, termed cross-beta structure. Using a group of chemically distinct polyamino acids, we show here that the existence of such a structure does not require the presence of specific side chain interactions or sequence patterns. These observations firmly establish that amyloid formation and protein folding represent two fundamentally different ways of organizing polypeptides into ordered conformations. Protein folding depends critically on the presence of distinctive side chain sequences and produces a unique globular fold. By contrast, the properties of different polyamino acids suggest that amyloid formation arises primarily from main chain interactions that are, in some environments, overruled by specific side chain contacts. This side chain effect can be thought of as the inverse of the one that characterizes protein folding. Conditions including Alzheimer's and Creutzfeldt-Jakob diseases represent, on this basis, pathological cases in which a natural polypeptide chain has aberrantly adopted the conformation that is primarily defined by main chain interactions and not the structure that is determined by specific side chain contacts that depend on the polypeptide sequence.
authors.affiliation: Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, South Parks Road, UK. fandrich@imb-jena.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000502:physiology*; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D002942:Circular Dichroism; D007700:Kinetics; D008854:Microscopy, Electron; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000596:Amino Acids; D000682:Amyloid