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Nature. 2014 Dec 11;516(7530):250-3. doi: 10.1038/nature13768. Epub 2014 Sep 14.

Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG.

Author information

1
1] Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium [2] Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
2
1] Unité G5 Biologie structurale de la sécrétion bactérienne, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France [2] UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France.
3
Structure et Fonction des Membranes Biologiques (SFMB), Université Libre de Bruxelles, 1050 Brussels, Belgium.
4
UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France.
5
Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St Louis, Missouri 63110-1010, USA.
6
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA.
7
Department of Chemistry, Institute for Structural and Molecular Biology, University College London, London WC1H 0AJ, UK.

Abstract

Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the α and γ classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded β-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 Å(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.

PMID:
25219853
PMCID:
PMC4268158
DOI:
10.1038/nature13768
[Indexed for MEDLINE]
Free PMC Article

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