Heating during agitation of β₂-microglobulin reveals that supersaturation breakdown is required for amyloid fibril formation at neutral pH.

ABSTRACT: Amyloidosis-associated amyloid fibrils are formed by denatured proteins when supersaturation of denatured proteins is broken. β₂-Microglobulin (β2m) forms amyloid fibrils and causes dialysis-related amyloidosis in patients receiving long-term hemodialysis. Although amyloid fibrils of β2m in patients are observed at neutral pH, formation of β2m amyloids in vitro has been difficult to discern at neutral pH because of the amyloid-resistant native structure. Here, to further understand the mechanism underlying in vivo amyloid formation, we investigated the relationship between protein folding/unfolding and misfolding leading to amyloid formation. Using thioflavin T assays, CD spectroscopy, and transmission EM analyses, we found that β2m efficiently forms amyloid fibril

SUBMITTER: Noji M 

PROVIDER: S-EPMC6816083 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature