A proposed structural model for amyloid fibril elongation: domain swapping forms an interdigitating {beta}-structure polymer

We propose a model illustrating how proteins, which differ intheir overall sequences and structures, can form the propagating,twisted ß-sheet conformations, characteristic of amyloids.Some cases of amyloid formation can be explained through a `domainswapping' event, where the swapped segment is either a ß-hairpinor an unstable conformation which can partially unfold and assumea ß-hairpin structure. As in domain swapping, herethe swapped ß-hairpin is at the edge of the structure,has few (if any) salt bridges and hydrogen bonds connectingit to the remainder of the structure and variable extents ofburied non-polar surface areas. Additionally, in both casesthe swapped piece constitutes a transient `building block' ofthe structure, with a high population time. Whereas in domainswapping the swapped fragment has been shown to be an