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

TitleStructural and mechanistic insights into the bacterial amyloid secretion channel CsgG.
Publication TypeJournal Article
Year of Publication2014
AuthorsGoyal, P., P. V. Krasteva, N. Van Gerven, F. Gubellini, I. Van den Broeck, A. Troupiotis-Tsaïlaki, W. Jonckheere, G. Péhau-Arnaudet, J. S. Pinkner, M. R. Chapman, S. J. Hultgren, S. Howorka, R. Fronzes, and H. Remaut
JournalNature
Volume516
Issue7530
Pagination250-3
Date Published2014 Dec 11
ISSN1476-4687
KeywordsAmyloid, Biofilms, Cell Membrane, Crystallography, X-Ray, Diffusion, Entropy, Escherichia coli, Escherichia coli Proteins, Lipoproteins, Membrane Transport Proteins, Models, Biological, Models, Molecular, Periplasm, Protein Conformation, Protein Transport
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.

DOI10.1038/nature13768
Alternate JournalNature
PubMed ID25219853
PubMed Central IDPMC4268158
Grant ListR01 AI048689 / AI / NIAID NIH HHS / United States
R01 AI073847 / AI / NIAID NIH HHS / United States
R01 AI099099 / AI / NIAID NIH HHS / United States
R56 AI073847 / AI / NIAID NIH HHS / United States
R01 A1073847 / / PHS HHS / United States
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