The role of conformational flexibility in β2-microglobulin amyloid fibril formation at neutral pH.

ABSTRACT:

Rationale

Amyloid formation is implicated in a number of human diseases. β(2)-Microglobulin (β(2)m) is the precursor protein in dialysis-related amyloidosis and it has been shown that partial, or more complete, unfolding is key to amyloid fibril formation in this pathology. Here the relationship between conformational flexibility and β(2)m amyloid formation at physiological pH has been investigated.

Methods

HDX-ESI-MS was used to study the conformational dynamics of β(2)m. Protein engineering, or the addition of Cu(2+) ions, sodium dodecyl sulphate, trifluoroethanol, heparin, or protein stabilisers, was employed to perturb the conformational dynamics of β(2)m. The fibril-forming propensities of the protein variants and the wild-type protein in the presence of additives, whic

SUBMITTER: Hodkinson JP 

PROVIDER: S-EPMC3568905 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature