|Title||Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Goyal, 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|
|Date Published||2014 Dec 11|
|Keywords||Amyloid, 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|
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.
|PubMed Central ID||PMC4268158|
|Grant List||R01 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
Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG.