Toward a Soluble Model System for the Amyloid State [component]

unpublished
General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: ABSTRACT: The 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
more » ... equence 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 inter-sheet 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.
doi:10.1021/jacs.7b07225.s001 fatcat:zenqqfdxvbe4nmiss65kbfpqy4