Structural Characterisation of Oligomeric Intermediates on Pathway to Amyloid Formation

摘要

The formation of insoluble amyloid fibrils in vivo is associated with over thirty different pathological conditions. Despite extensive studies, the mechanism by which these proteins assemble into highly ordered, cross-beta structures remains elusive. Beta-2 microglobulin is a 99-residue protein, whose aggregation is associated with the disease, dialysis-related amyloidosis. Incubation of beta-2 microglobulin under physiological conditions in vitro does not lead to fibril formation, however fibrillogenesis can be initiated at low pH, yielding amyloid fibrils of similar morphology to those detected in vivo.