The identification and characterization of oligomers preceding the formation of fibrils is of particular interest because of an increasing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. We selected Xaperones that block the fibrillogenesis of a proteolytic amyloidogenic ΔN6 variant of β2m (blue). We found that one of the fibrillogenesis inhibitors (red) traps a domain swapped dimer of ΔN6β2m in the crystal. The crystal structure of this dimer has several properties that have been attributed to prefibrillar intermediates of β2m fibrillogenesis.

Domanska K, Vanderhaegen S, Srinivasan V, Pardon E & Dupeux F, Marquez JK, Giorgetti S, Stoppini M, Wyns L, Bellotti V, & Steyaert J (2011) Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic β2-microglobulin variant. PNAS. Published online before print.