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.

Secondary

Biomolecular

Nuclear Magnetic Resonance

Mice

Escherichia coli Proteins

Humans

Pathological

metabolism

Animals

metabolism

Protein Structure

Molecular Chaperones

Protein Aggregation

metabolism

Protein Binding

genetics

metabolism

alpha-Synuclein

Membrane Transport Proteins

chemistry

Recombinant Fusion Proteins

Protein Multimerization

metabolism

genetics

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)

Vol. 10 10 e0140194-

Subject Categories

Biological Sciences

Biophysics

DOI

10.1371/journal.pone.0140194

PubMed

26465894

More information

Latest update

4/20/2018