β arcades: recurring motifs in naturally occurring and disease‐related amyloid fibrils

Amyloid fibrils are filamentous protein aggregates that accumulate in diseases such as Alzheimer's or type II diabetes. The amyloid‐forming protein is disease specific. Amyloids may also be formed in vitro from many other proteins, after first denaturing them. Unlike the diverse native folds of these proteins, their amyloids are fundamentally similar in being rigid, smooth‐sided, and cross‐β‐structured, that is, with β strands running perpendicular to the fibril axis. In the absence of high‐resolution fibril structures, increasingly credible models are being derived by integrating data from a crossfire of experimental techniques. Most current models of disease‐related amyloids invoke “β arcades,” columnar structures produced by in‐register stacking of “β arches.” A β arch is a strand‐turn‐strand motif in which the two β strands interact via their side chains, not via the polypeptide backbone as in a conventional β hairpin. Crystal structures of β‐solenoids, a class of proteins with amyloid‐like properties, offer insight into the β‐arc turns found in β arches. General conformational and thermodynamic considerations suggest that complexes of 2 or more β arches may nucleate amyloid fibrillogenesis in vivo. The apparent prevalence of β arches and their components have implications for identifying amyloidogenic sequences, elucidating fibril polymorphisms, predicting the locations and conformations of β arcs within amyloid fibrils, and refining existing fibril models.—Kajava, A. V., Baxa, U., Steven, A. C. β arcades: recurring motifs in naturally occurring and disease‐related amyloid fibrils. FASEB J. 24, 1311–1319 (2010). www.fasebj.org