Copper chaperone blocks amyloid formation via ternary complex
Review article, 2018

Protein misfolding in cells is avoided by a network of protein chaperones that detect misfolded or partially folded species. When proteins escape these control systems, misfolding may result in protein aggregation and amyloid formation. We here show that aggregation of the amyloidogenic protein alpha-synuclein (alpha S), the key player in Parkinson's disease, is controlled by the copper transport protein Atox1 in vitro. Copper ions are not freely available in the cellular environment, but when provided by Atox1, the resulting copper-dependent ternary complex blocks aS aggregation. Because the same inhibition was found for a truncated version of alpha S, lacking the C-terminal part, it appears that Atox1 interacts with the N-terminal copper site in alpha S. Metal-dependent chaperoning may be yet another manner in which cells control its proteome.

copper chaperone

metal transport

Alpha-synuclein

amyloids

Atox1

protein misfolding

Author

Istvan Horvath

Chalmers, Biology and Biological Engineering, Chemical Biology

Tony Werner

Chalmers, Biology and Biological Engineering, Chemical Biology

Ranjeet Kumar

Chalmers, Biology and Biological Engineering, Chemical Biology

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Quarterly Reviews of Biophysics

0033-5835 (ISSN) 1469-8994 (eISSN)

Vol. 51 e6

Subject Categories

Biochemistry and Molecular Biology

Biophysics

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1017/S0033583518000045

More information

Latest update

1/18/2019