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Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones

Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC po...

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Autores principales: Taylor, Jonathan D., Hawthorne, William J., Lo, Joanne, Dear, Alexander, Jain, Neha, Meisl, Georg, Andreasen, Maria, Fletcher, Catherine, Koch, Marion, Darvill, Nicholas, Scull, Nicola, Escalera-Maurer, Andrés, Sefer, Lea, Wenman, Rosemary, Lambert, Sebastian, Jean, Jisoo, Xu, Yingqi, Turner, Benjamin, Kazarian, Sergei G., Chapman, Matthew R., Bubeck, Doryen, de Simone, Alfonso, Knowles, Tuomas P. J., Matthews, Steve J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838910/
https://www.ncbi.nlm.nih.gov/pubmed/27098162
http://dx.doi.org/10.1038/srep24656
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author Taylor, Jonathan D.
Hawthorne, William J.
Lo, Joanne
Dear, Alexander
Jain, Neha
Meisl, Georg
Andreasen, Maria
Fletcher, Catherine
Koch, Marion
Darvill, Nicholas
Scull, Nicola
Escalera-Maurer, Andrés
Sefer, Lea
Wenman, Rosemary
Lambert, Sebastian
Jean, Jisoo
Xu, Yingqi
Turner, Benjamin
Kazarian, Sergei G.
Chapman, Matthew R.
Bubeck, Doryen
de Simone, Alfonso
Knowles, Tuomas P. J.
Matthews, Steve J.
author_facet Taylor, Jonathan D.
Hawthorne, William J.
Lo, Joanne
Dear, Alexander
Jain, Neha
Meisl, Georg
Andreasen, Maria
Fletcher, Catherine
Koch, Marion
Darvill, Nicholas
Scull, Nicola
Escalera-Maurer, Andrés
Sefer, Lea
Wenman, Rosemary
Lambert, Sebastian
Jean, Jisoo
Xu, Yingqi
Turner, Benjamin
Kazarian, Sergei G.
Chapman, Matthew R.
Bubeck, Doryen
de Simone, Alfonso
Knowles, Tuomas P. J.
Matthews, Steve J.
author_sort Taylor, Jonathan D.
collection PubMed
description Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid inhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservation of conformational flexibility also enables efficient secretion to the cell surface. Understanding how bacteria safely handle amyloidogenic polypeptides contribute towards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications.
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spelling pubmed-48389102016-04-27 Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones Taylor, Jonathan D. Hawthorne, William J. Lo, Joanne Dear, Alexander Jain, Neha Meisl, Georg Andreasen, Maria Fletcher, Catherine Koch, Marion Darvill, Nicholas Scull, Nicola Escalera-Maurer, Andrés Sefer, Lea Wenman, Rosemary Lambert, Sebastian Jean, Jisoo Xu, Yingqi Turner, Benjamin Kazarian, Sergei G. Chapman, Matthew R. Bubeck, Doryen de Simone, Alfonso Knowles, Tuomas P. J. Matthews, Steve J. Sci Rep Article Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid inhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservation of conformational flexibility also enables efficient secretion to the cell surface. Understanding how bacteria safely handle amyloidogenic polypeptides contribute towards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications. Nature Publishing Group 2016-04-21 /pmc/articles/PMC4838910/ /pubmed/27098162 http://dx.doi.org/10.1038/srep24656 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Taylor, Jonathan D.
Hawthorne, William J.
Lo, Joanne
Dear, Alexander
Jain, Neha
Meisl, Georg
Andreasen, Maria
Fletcher, Catherine
Koch, Marion
Darvill, Nicholas
Scull, Nicola
Escalera-Maurer, Andrés
Sefer, Lea
Wenman, Rosemary
Lambert, Sebastian
Jean, Jisoo
Xu, Yingqi
Turner, Benjamin
Kazarian, Sergei G.
Chapman, Matthew R.
Bubeck, Doryen
de Simone, Alfonso
Knowles, Tuomas P. J.
Matthews, Steve J.
Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title_full Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title_fullStr Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title_full_unstemmed Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title_short Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones
title_sort electrostatically-guided inhibition of curli amyloid nucleation by the csgc-like family of chaperones
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838910/
https://www.ncbi.nlm.nih.gov/pubmed/27098162
http://dx.doi.org/10.1038/srep24656
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