ja7b07225_si_001.pdf (5.76 MB)
Toward a Soluble Model System for the Amyloid State
journal contribution
posted on 2017-11-08, 20:18 authored by Nicole
C. Thomas, Gail J. Bartlett, Derek N. Woolfson, Samuel H. GellmanThe formation and
deposition of amyloids is associated with many
diseases. β-Sheet secondary structure is a common feature of
amyloids, but the packing of sheets against one another is distinctive
relative to soluble proteins. Standard methods that rely on perturbing
a polypeptide’s sequence and evaluating impact on folding can
be problematic for amyloid aggregates because a single sequence can
adopt multiple conformations and diverse packing arrangements. We
describe initial steps toward a minimum-sized, soluble model system
for the amyloid state that supports comparisons among sequence variants.
Critical to this goal is development of a new linking strategy to
enable intersheet association mediated by side chain interactions,
which is characteristic of the amyloid state. The linker design we
identified should ultimately support exploration of relationships
between sequence and amyloid state stability for specific strand-association
modes.