The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4.

ABSTRACT: The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain. This unusual domain is comprised of four or more tandem repeats of the fundamental sequence PHGGGWGQ. Previous work from our laboratories demonstrates that at full copper occupancy, each HGGGW segment binds a single Cu2+. However, several recent studies suggest that low copper occupancy favors different coordination modes, possibly involving imidazoles from histidines in adjacent octapeptide segments. This is investigated here using a combination of X-band EPR, S-band EPR, and ESEEM, along with a library of modified peptides designed to favor different coordination interactions. At pH 7.4, three distinct coordination modes are identified. Each mode is fully characterized to reveal a series of copper-dependent octarepea

SUBMITTER: Chattopadhyay M 

PROVIDER: S-EPMC2909831 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature