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Mol Cell. 2015 Feb 5;57(3):445-55. doi: 10.1016/j.molcel.2014.12.025. Epub 2015 Jan 22.

The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.

Author information

1
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
2
Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
3
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
4
Centre for Microbial Research, Umeå University, 901 87 Umeå, Sweden; Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
5
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA; Centre for Microbial Research, Umeå University, 901 87 Umeå, Sweden. Electronic address: chapmanm@umich.edu.

Abstract

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.

PMID:
25620560
PMCID:
PMC4320674
DOI:
10.1016/j.molcel.2014.12.025
[Indexed for MEDLINE]
Free PMC Article

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