Biology of amyloid: structure, function, and regulation.
Amyloids are highly ordered cross-β sheet protein aggregates associated with many diseases including Alzheimer's disease, but also with biological functions such as hormone storage. The cross-β sheet entity comprising an indefinitely repeating intermolecular β sheet motif is unique among protein folds. It grows by recruitment of the corresponding amyloid protein, while its repetitiveness can translate what would be a nonspecific activity as monomer into a potent one through cooperativity. Furthermore, the one-dimensional crystal-like repeat in the amyloid provides a structural framework for polymorphisms. This review summarizes the recent high-resolution structural studies of amyloid fibrils in light of their biological activities. We discuss how the unique properties of amyloids gives rise to many activities and further speculate about currently undocumented biological roles for the amyloid entity. In particular, we propose that amyloids could have existed in a prebiotic world, and may have been the first functional protein fold in living cells.
Greenwald
Jason
J
ETH Zurich, Physical Chemistry, ETH Honggerberg, 8093 Zurich, Switzerland.
Riek
Roland
R
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019418:Evolution, Chemical; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)