Functional and pathological amyloid structures in the eyes of 2020 cryo-EM

Abstract

The amyloid state of protein aggregation is associated with neurodegenerative and systemic diseases but can play physiological roles in many organisms, including as stress granules and virulence determinants. The recent resolution revolution in cryogenic electron microscopy (cryo-EM) has significantly expanded the repertoire of high-resolution amyloid structures, to include, for the first-time, fibrils extracted ex vivo in addition to those formed, or seeded, in vitro. Here, we review recently solved cryo-EM amyloid structures, and compare amino acid prevalence, in efforts to systematically distinguish between pathological and functional amyloids, even though such structural classification is hindered by extensive polymorphism even among fibrils of the same protein, and by dual functioning of some human amyloids in both physiological activities and disease mechanisms. Forthcoming structures of bacterial amyloids may expose specific, evolutionary-designed properties specific to functional fibrils.