Molecular basis for the Cu2+ binding-induced destabilization of beta2-microglobulin revealed by molecular dynamics simulation.

ABSTRACT: According to experimental data, binding of the Cu(2+) ions destabilizes the native state of beta2-microglobulin (beta2m). The partial unfolding of the protein was generally considered an early step toward fibril formation in dialysis-related amyloidosis. Recent NMR studies have suggested that the destabilization of the protein might be achieved through increased flexibility upon Cu(2+) binding. However, the molecular mechanism of destabilization due to Cu(2+), its role in amyloid formation, and the relative contributions of different potential copper-binding sites remain unclear. To elucidate the effect of ion ligation at atomic detail, a series of molecular dynamics simulations were carried out on apo- and Cu(2+)-beta2m systems in explicit aqueous solutions, with varying numbers of bound

SUBMITTER: Deng NJ 

PROVIDER: S-EPMC1459522 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature