The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.
Artikel i vetenskaplig tidskrift, 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.

genetics

Escherichia coli

metabolism

pharmacology

Humans

Base Sequence

metabolism

metabolism

Escherichia coli Proteins

metabolism

chemistry

chemistry

genetics

Amino Acid Motifs

In Vitro Techniques

Molecular Sequence Data

Protein Structure

alpha-Synuclein

Secondary

drug effects

Protein Aggregates

Amyloid beta-Peptides

Författare

Margery L Evans

E. Chorell

Jonathan D Taylor

J. Åden

Anna Götheson

Fei Li

Marion Koch

Lea Sefer

Steve J Matthews

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

F. Almqvist

Matthew R Chapman

Molecular Cell

1097-2765 (ISSN) 1097-4164 (eISSN)

Vol. 57 445-55

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Biofysik

DOI

10.1016/j.molcel.2014.12.025

PubMed

25620560