Abstract
Amyloids are highly ordered protein aggregates that are associated with both disease (including PrP prion, Alzheimer's, and Parkinson's) and biological function. The amyloid structure is composed of the cross-β-sheet entity, which is an almost indefinitely repeating two-layered intermolecular β-sheet motif. The three-dimensional (3D) structure is unique among protein folds because it folds only upon intermolecular contacts (for a folding to occur, only short sequences of amino acid residues are required), and the structure repeats itself at the atomic level (i.e., every 4.7 Å). As a consequence of this structure, among others, it can grow by recruiting corresponding amyloid peptide/protein and thus has the capacity to be an infectious protein (i.e., a prion). Furthermore, its repetitiveness can translate what would be a nonspecific activity as monomer into a potent one through cooperativity. Because of these and other properties, the activities of amyloids are manifold and include peptide storage, template assistance, loss of function, gain of function, generation of toxicity, membrane binding, infectivity, and more. This review summarizes the structural nature of the cross-β-sheet motif on the basis of a few high-resolution structural studies of amyloids in the context of potential biological activities.