Probing Transient Non-Native States in Amyloid Beta Fiber Elongation by NMR

Using NMR to probe transient binding of Aβ1–40 monomers to fibers, we find partially bound conformations with the highest degree of interaction near F19–K28 and a lesser degree of interaction near the C-terminus (L34–G37). This represents a shift away from the KLVFFA recognition sequence (residues 16–21) currently used for inhibitor design.