Copper chaperone blocks amyloid formation via ternary complex
Reviewartikel, 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.

amyloids

Alpha-synuclein

protein misfolding

metal transport

Atox1

copper chaperone

Författare

Istvan Horvath

Chalmers, Biologi och bioteknik, Kemisk biologi

Tony Werner

Chalmers, Biologi och bioteknik, Kemisk biologi

Ranjeet Kumar

Chalmers, Biologi och bioteknik, Kemisk biologi

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Quarterly Reviews of Biophysics

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

Vol. 51 e6

Ämneskategorier

Biokemi och molekylärbiologi

Biofysik

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1017/S0033583518000045

PubMed

30912493

Mer information

Senast uppdaterat

2019-06-24