Beta 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-beta-structured, that is, with beta 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 "beta arcades," columnar structures produced by in-register stacking of "beta arches." A beta arch is a strand-turn-strand motif in which the two beta strands interact via their side chains, not via the polypeptide backbone as in a conventional beta hairpin. Crystal structures of beta-solenoids, a class of proteins with amyloid-like properties, offer insight into the beta-arc turns found in beta arches. General conformational and thermodynamic considerations suggest that complexes of 2 or more beta arches may nucleate amyloid fibrillogenesis in vivo. The apparent prevalence of beta arches and their components have implications for identifying amyloidogenic sequences, elucidating fibril polymorphisms, predicting the locations and conformations of beta arcs within amyloid fibrils, and refining existing fibril models.
Kajava
Andrey V
AV
Centre de Recherches de Biochimie Macromoléculaire, CNRS, University of Montpellier 1 and 2, Montpellier, France.
Baxa
Ulrich
U
Steven
Alasdair C
AC
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D000682:Amyloid