Figure 7. Exchange of Aβ monomer on the surface of large polydisperse protofibrils studied by ¹⁵N lifetime line broadening (Δ/R₂) and ¹⁵N-DEST.

(A) Kinetic schemes for Aβ monomer exchange on the surface of amyloid protofibrils in which the protofibril-bound peptide (M_oligomer) exists in only a single state (top), or a large ensemble of states such that each residue can be either tethered or in direct contact with the surface of the oligomer with K₃(i)=k₂ (app) (i)/k_i (app) (i) (bottom). The circle in the diagrammatic representation of the states represents a single residue that is either tethered or in direct contact and for which three possible chain configurations are shown. (B) ¹⁵N-DEST profiles for Leu¹⁷ and Asn²⁷ at two radiofrequency (RF) fields (170 Hz, orange; 350 Hz, blue) with the experimental points shown as circles, and the best-fit curves obtained with the single state or ensemble of states models shown as dashed and continuous lines respectively. (C) Comparison of the experimental ¹⁵N-ΔR₂ profile (black closed circles) with the calculated profiles obtained with the single state (grey open circles) and ensemble of states (blue open circles) models. (D) Profiles for the residue-specific partition coefficient K₃ (given by the ratio of direct contact to tethered states; see A, bottom panel) and ¹⁵N-R₂ values for the tethered states derived from the fits to the experimental ΔR₂ and DEST data. Adapted from Fawzi, N.L., Ying, J., Ghirlando, R., Torchia, D.A. and Clore, G.M. (2011) Atomic-resolution dynamics on the surface of amyloid-^ protofibrils probed by solution NMR. Nature 480, 268–272 with permission.