Journal
MOLECULAR CELL
Volume 57, Issue 3, Pages 445-455Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2014.12.025
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Funding
- NIH [AI073847-6]
- University of Michigan Cellular Biotechnology Training Program [NIH NRSA T32 GM008353]
- University of Michigan Rackham Graduate School Predoctoral Fellowship
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Wallenberg Foundation
- Goran Gustafsson Foundation
- Wellcome Trust
- Wellcome Trust [100280/Z/12/Z] Funding Source: Wellcome Trust
- MRC [G1001664, MR/J006874/1] Funding Source: UKRI
- Medical Research Council [G1001664, 1365661] Funding Source: researchfish
- Wellcome Trust [100280/Z/12/Z] Funding Source: researchfish
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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-beta-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human alpha-synuclein, but not A beta(42), in vitro. We identified a common D-Q-Phi-X-0,X-1-G-K-N-zeta-E motif in CsgC client proteins that is not found in A beta(42). 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.
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