title: Amyloid structure and assembly: insights from scanning transmission electron microscopy.
abstract: Amyloid fibrils are filamentous protein aggregates implicated in several common diseases such as Alzheimer's disease and type II diabetes. Similar structures are also the molecular principle of the infectious spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans, scrapie in sheep, and of the so-called yeast prions, inherited non-chromosomal elements found in yeast and fungi. Scanning transmission electron microscopy (STEM) is often used to delineate the assembly mechanism and structural properties of amyloid aggregates. In this review we consider specifically contributions and limitations of STEM for the investigation of amyloid assembly pathways, fibril polymorphisms and structural models of amyloid fibrils. This type of microscopy provides the only method to directly measure the mass-per-length (MPL) of individual filaments. Made on both in vitro assembled and ex vivo samples, STEM mass measurements have illuminated the hierarchical relationships between amyloid fibrils and revealed that polymorphic fibrils and various globular oligomers can assemble simultaneously from a single polypeptide. The MPLs also impose strong constraints on possible packing schemes, assisting in molecular model building when combined with high-resolution methods like solid-state nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR).
authors.affiliation: The Brain and Mind Research Institute, University of Sydney, NSW 2006, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Goldsbury
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baxa
authors.forename: Martha N
authors.initials: MN
authors.lastname: Simon
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
authors.forename: Andreas
authors.initials: A
authors.lastname: Engel
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Wall
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Müller
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D003704:Dementia / Q000473:pathology*; D006801:Humans; D017348:Microscopy, Electron, Scanning Transmission / Q000379:methods*; D008958:Models, Molecular; D010641:Phenotype
chemical_list: D000682:Amyloid