Delineating the conformational elements responsible for Cu(2+)-induced oligomerization of beta-2 microglobulin.

ABSTRACT: Beta-2 microglobulin (beta2m) is a small globular protein implicated in amyloid fiber formation in renal patients on long-term hemodialysis therapy. In vitro, under physiological conditions, beta2m is not aggregation prone. However, in the presence of stoichiometric Cu(2+), beta2m readily self-associates ultimately leading to heterogeneously sized aggregates. As this process occurs under near physiological solution conditions where the fold is >or=20 kJ/mol stabilized over the unfolded state, local conformational rearrangements are critical to understanding the oligomerization of beta2m. The isomerization of a conserved cis proline at residue 32 is a recognized step in this process that can be initiated by Cu(2+) binding. To better understand the structural basis of metal-induced oligomeri

SUBMITTER: Blaho DV 

PROVIDER: S-EPMC3342574 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature