Increased β-Sheet Dynamics and D-E Loop Repositioning Are Necessary for Cu(II)-Induced Amyloid Formation by β-2-Microglobulin.

ABSTRACT: β-2-Microglobulin (β2m) forms amyloid fibrils in the joints of patients undergoing dialysis treatment as a result of kidney failure. One of the ways in which β2m can be induced to form amyloid fibrils in vitro is via incubation with stoichiometric amounts of Cu(II). To better understand the structural changes caused by Cu(II) binding that allow β2m to form amyloid fibrils, we compared the effect of Ni(II) and Zn(II) binding, which are two similarly sized divalent metal ions that do not induce β2m amyloid formation. Using hydrogen/deuterium exchange mass spectrometry (HDX/MS) and covalent labeling MS, we find that Ni(II) has little effect on β2m structure, despite binding in the same region of the protein as Cu(II). This observation indicates that subtle differences in the organization of r

SUBMITTER: Borotto NB 

PROVIDER: S-EPMC5385854 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature