Structural characterization of prefibrillar intermediates and amyloid fibrils by small-angle X-ray scattering.

ABSTRACT

Structural investigation of the species present during protein fibrillation is of tremendous importance, yet complicated by the equilibrium between species of very different sizes and life-times. Small-angle X-ray scattering may be applied to solve this problem, providing both information about the process (number of species present and volume fractions of individual species) and low-resolution three-dimensional shape reconstructions of individual species. Here, we describe in detail the challenges associated with the approach, exemplified using data from fibrillating insulin or α-synuclein samples.