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.

Amyloid beta-Peptides

Escherichia coli

metabolism

alpha-Synuclein

Secondary

chemistry

metabolism

metabolism

drug effects

Escherichia coli Proteins

genetics

Protein Aggregates

In Vitro Techniques

Humans

Base Sequence

chemistry

Protein Structure

metabolism

genetics

Molecular Sequence Data

pharmacology

Amino Acid Motifs

Författare

Margery L Evans

University of Michigan

E. Chorell

Umeå universitet

Jonathan D Taylor

Imperial College London

J. Åden

Umeå universitet

Anna Götheson

Umeå universitet

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 universitet

F. Almqvist

Umeå universitet

Matthew R Chapman

Umeå universitet

University of Michigan

Molecular Cell

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

Vol. 57 3 445-55

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Biofysik

DOI

10.1016/j.molcel.2014.12.025

PubMed

25620560

Mer information

Senast uppdaterat

2019-06-12