Modeling by assembly and molecular dynamics simulations of the low Cu2+ occupancy form of the mammalian prion protein octarepeat region: gaining insight into Cu2+-mediated beta-cleavage.

ABSTRACT: The prion protein has garnered considerable interest because of its involvement in prion disease as well as its unresolved cellular function. The octarepeat region in the flexible N-domain is capable of binding copper through multiple coordination modes. Under conditions of low pH and low Cu(2+) concentration, the four octarepeats (ORs) cooperatively coordinate a single copper ion. Based on the average structure of the PHGG and GWGQ portions of a copper-free OR(2) model from molecular dynamics simulations, the starting structures of the OR(4) complex could be constructed by assembling the repeating structure of PHGG and GWGQ fragments. The resulting model contains a preformed site suitable for Cu(2+) coordination. Molecular dynamics simulations of Cu(2+) bound to the assembled OR(4) model

SUBMITTER: Pushie MJ 

PROVIDER: S-EPMC2586590 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature