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.
genetics
Secondary
Mice
Nuclear Magnetic Resonance
Humans
Molecular Chaperones
Protein Multimerization
Biomolecular
alpha-Synuclein
chemistry
Membrane Transport Proteins
Escherichia coli Proteins
Recombinant Fusion Proteins
metabolism
metabolism
Protein Aggregation
Pathological
Protein Structure
Animals
metabolism
metabolism
genetics
metabolism
Protein Binding
Author
E. Chorell
Umea universitet
Emma Andersson
Umea universitet
Margery L Evans
University Michigan Ann Arbor
Neha Jain
University Michigan Ann Arbor
Anna Götheson
Umea universitet
J. Åden
Umea universitet
Matthew R Chapman
University Michigan Ann Arbor
F. Almqvist
Umea universitet
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
PLoS ONE
1932-6203 (ISSN)
Vol. 10 10 e0140194-Subject Categories (SSIF 2011)
Biological Sciences
Biophysics
DOI
10.1371/journal.pone.0140194
PubMed
26465894