Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts.
Journal article, 2015
Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein α-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical α-synuclein oligomers. We find that CsgE also modulates α-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates α-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.
Protein Aggregation
Protein Binding
metabolism
Recombinant Fusion Proteins
Pathological
metabolism
Protein Structure
metabolism
chemistry
Mice
Protein Multimerization
metabolism
Biomolecular
genetics
Escherichia coli Proteins
Nuclear Magnetic Resonance
Animals
genetics
alpha-Synuclein
Humans
Membrane Transport Proteins
Secondary
Molecular Chaperones
metabolism
Author
E. Chorell
Umeå University
Emma Andersson
Umeå University
Margery L Evans
University of Michigan
Neha Jain
University of Michigan
Anna Götheson
Umeå University
J. Åden
Umeå University
Matthew R Chapman
University of Michigan
F. Almqvist
Umeå University
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 10 10 e0140194- A1004Subject Categories
Biological Sciences
Biophysics
DOI
10.1371/journal.pone.0140194
PubMed
26465894