Structural Heterogeneity in the Preamyloid Oligomers of β-2-Microglobulin.

ABSTRACT: In dialysis patients, the protein β2-microglobulin (β2m) forms amyloid fibrils in a condition known as dialysis-related amyloidosis. To understand the early stages of the amyloid assembly process, we have used native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble preamyloid oligomers. ESI-IM-MS reveals the presence of multiple conformers for the dimer, tetramer, and hexamer that precede the Cu(II)-induced amyloid assembly process, results which are distinct from β2m oligomers formed at low pH. Experimental and computational results indicate that the predominant dimer is a Cu(II)-bound structure with an antiparallel side-by-side configuration. In contrast, tetramers exist in solution in both Cu(II)-bound and Cu(II)-free forms. Selective d

SUBMITTER: Marcinko TM 

PROVIDER: S-EPMC6995769 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature