The bacterial curli system possesses a potent and selective inhibitor of amyloid formation
Journal article, 2015
Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.
Secondary
Base Sequence
drug effects
Amyloid beta-Peptides
genetics
pharmacology
alpha-Synuclein
metabolism
chemistry
metabolism
Protein Aggregates
genetics
Escherichia coli
Amino Acid Motifs
Humans
metabolism
chemistry
In Vitro Techniques
Protein Structure
Molecular Sequence Data
metabolism
Escherichia coli Proteins
Author
Margery L Evans
University of Michigan
E. Chorell
Umeå University
Jonathan D Taylor
Imperial College London
J. Åden
Umeå University
Anna Götheson
Umeå University
Fei Li
University of Michigan
Marion Koch
Imperial College London
Lea Sefer
Imperial College London
Steve J Matthews
Imperial College London
Pernilla Wittung Stafshede
Umeå University
F. Almqvist
Umeå University
Matthew R Chapman
Umeå University
University of Michigan
Molecular Cell
1097-2765 (ISSN) 1097-4164 (eISSN)
Vol. 57 3 445-455Subject Categories
Cell Biology
Biochemistry and Molecular Biology
Biophysics
DOI
10.1016/j.molcel.2014.12.025
PubMed
25620560