Copper mediated amyloid-β binding to Transthyretin.

ABSTRACT: Transthyretin (TTR), a homotetrameric protein that transports thyroxine and retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural protective response against Alzheimer's disease (AD), modulates amyloid-β (Aβ) deposition by direct interaction and co-localizes with Aβ in plaques. TTR levels are lower in the CSF of AD patients. Zn²⁺, Mn²⁺ and Fe²⁺ transform TTR into a protease able to cleave Aβ. To explain these activities, monomer dissociation or conformational changes have been suggested. Here, we report that when TTR crystals are exposed to copper or iron salts, the tetramer undergoes a significant conformational change that alters the dimer-dimer interface and rearranges residues implicated in TTR's ability to neutralize Aβ. We also de

SUBMITTER: Ciccone L 

PROVIDER: S-EPMC6137083 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature