posted on 2024-02-13, 08:30authored byKent R. Thurber, Wai-Ming Yau, Robert Tycko
Polypeptides
often self-assemble to form amyloid fibrils,
which
contain cross-β structural motifs and are typically 5–15
nm in width and micrometers in length. In many cases, short segments
of longer amyloid-forming protein or peptide sequences also form cross-β
assemblies but with distinctive ribbon-like morphologies that are
characterized by a well-defined thickness (on the order of 5 nm) in
one lateral dimension and a variable width (typically 10–100
nm) in the other. Here, we use a novel combination of data from solid-state
nuclear magnetic resonance (ssNMR), dark-field transmission electron
microscopy (TEM), atomic force microscopy (AFM), and cryogenic electron
microscopy (cryoEM) to investigate the structures within amyloid ribbons
formed by residues 14–23 and residues 11–25 of the Alzheimer’s
disease-associated amyloid-β peptide (Aβ14–23 and Aβ11–25). The ssNMR data indicate antiparallel
β-sheets with specific registries of intermolecular hydrogen
bonds. Mass-per-area values are derived from dark-field TEM data.
The ribbon thickness is determined from AFM images. For Aβ14–23 ribbons, averaged cryoEM images show a periodic
spacing of β-sheets. The combined data support structures in
which the amyloid ribbon growth direction is the direction of intermolecular
hydrogen bonds between β-strands, the ribbon thickness corresponds
to the width of one β-sheet (i.e., approximately the length
of one molecule), and the variable ribbon width is a variable multiple
of the thickness of one β-sheet (i.e., a multiple of the repeat
distance in a stack of β-sheets). This architecture for a cross-β
assembly may generally exist within amyloid ribbons.