Copper chaperone blocks amyloid formation via ternary complex. (9th May 2018)

• Record Type: Journal Article
• Authors: Horvath, Istvan; Werner, Tony; Kumar, Ranjeet; Wittung-Stafshede, Pernilla
• Is Part Of: Quarterly reviews of biophysics. Volume 51(2018)
• Publication Date: 2018-05-09
• Subjects: Alpha-synuclein, -- amyloids, -- Atox1, -- copper chaperone, -- metal transport, -- protein misfolding; Biophysics -- Periodicals; 571.405
• DOI: 10.1017/S0033583518000045
• Languages: English
• ISSNs: 0033-5835

Abstract

Abstract: 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 α -synuclein ( α 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 α S aggregation. Because the same inhibition was found for a truncated version of α S, lacking the C-terminal part, it appears that Atox1 interacts with the N-terminal copper site in α S. Metal-dependent chaperoning may be yet another manner in which cells control its proteome.