X-ray Absorption Spectroscopy Investigations of Copper(II) Coordination in the Human Amyloid β Peptide.

Alzheimer's disease (AD) is the main cause of age-related dementia and currently affects approximately 5.7 million Americans. Major brain changes associated with AD pathology include accumulation of amyloid beta (Aβ) protein fragments and formation of extracellular amyloid plaques.

Molecular Features of the Zn Binding Site in the Prion Protein Probed by Cd NMR.

The cellular prion protein (PrP) is a zinc-binding protein that contributes to the regulation of Zn and other divalent species of the central nervous system. Zn coordinates to the flexible, N-terminal repeat region of PrP and drives a tertiary contact between this repeat region and a well-defined cleft of the C-terminal domain. The tertiary structure promoted by Zn is thought to regulate inherent PrP toxicity.

Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation.

Copper plays a critical role in prion protein (PrP) physiology. Cu(2+) binds with high affinity to the PrP N-terminal octarepeat (OR) domain, and intracellular copper promotes PrP expression. The molecular details of copper coordination within the OR are now well characterized.