@article{Taylor:2016:10.1038/srep24656,
author = {Taylor, JD and Hawthorne, WJ and Lo, J and Dear, A and Jain, N and Meisl, G and Andreasen, M and Fletcher, C and Koch, M and Darvill, N and Scull, N and Escalera-Maurer, A and Sefer, L and Wenman, R and Lambert, S and Jean, J and Xu, Y and Turner, B and Kazarian, SG and Chapman, MR and Bubeck, D and de, Simone A and Knowles, TPJ and Matthews, SJ},
doi = {10.1038/srep24656},
journal = {Scientific Reports},
title = {Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones},
url = {http://dx.doi.org/10.1038/srep24656},
volume = {6},
year = {2016}
}

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TY  - JOUR
AB  - Polypeptide aggregation into amyloid is linked with several debilitating human diseases.Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export ofamyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. AnEscherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins.Here we unlock its mechanism of action, and show that CsgC strongly inhibits primarynucleation via electrostatically-guided molecular encounters, which expands theconformational distribution of disordered curli subunits. This delays the formation of higherorder intermediates and maintains amyloidogenic subunits in a secretion-competent form.New structural insight also reveal that CsgC is part of diverse family of bacterial amyloidinhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservationof conformational flexibility also enables efficient secretion to the cellsurface. Understanding how bacteria safely handle amyloidogenic polypeptides contributetowards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications.
AU  - Taylor,JD
AU  - Hawthorne,WJ
AU  - Lo,J
AU  - Dear,A
AU  - Jain,N
AU  - Meisl,G
AU  - Andreasen,M
AU  - Fletcher,C
AU  - Koch,M
AU  - Darvill,N
AU  - Scull,N
AU  - Escalera-Maurer,A
AU  - Sefer,L
AU  - Wenman,R
AU  - Lambert,S
AU  - Jean,J
AU  - Xu,Y
AU  - Turner,B
AU  - Kazarian,SG
AU  - Chapman,MR
AU  - Bubeck,D
AU  - de,Simone A
AU  - Knowles,TPJ
AU  - Matthews,SJ
DO  - 10.1038/srep24656
PY  - 2016///
SN  - 2045-2322
TI  - Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep24656
UR  - http://hdl.handle.net/10044/1/30601
VL  - 6
ER  - 

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