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Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties

Engineering functional amyloids through a modular genetic strategy represents new opportunities for creating multifunctional molecular materials with tailored structures and performance. Despite important advances, how fusion modules affect the self-assembly and functional properties of amyloids rem...

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Autores principales: Cui, Mengkui, Qi, Qi, Gurry, Thomas, Zhao, Tianxin, An, Bolin, Pu, Jiahua, Gui, Xinrui, Cheng, Allen A., Zhang, Siyu, Xun, Dongmin, Becce, Michele, Briatico-Vangosa, Francesco, Liu, Cong, Lu, Timothy K., Zhong, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461117/
https://www.ncbi.nlm.nih.gov/pubmed/31015941
http://dx.doi.org/10.1039/c9sc00208a
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author Cui, Mengkui
Qi, Qi
Gurry, Thomas
Zhao, Tianxin
An, Bolin
Pu, Jiahua
Gui, Xinrui
Cheng, Allen A.
Zhang, Siyu
Xun, Dongmin
Becce, Michele
Briatico-Vangosa, Francesco
Liu, Cong
Lu, Timothy K.
Zhong, Chao
author_facet Cui, Mengkui
Qi, Qi
Gurry, Thomas
Zhao, Tianxin
An, Bolin
Pu, Jiahua
Gui, Xinrui
Cheng, Allen A.
Zhang, Siyu
Xun, Dongmin
Becce, Michele
Briatico-Vangosa, Francesco
Liu, Cong
Lu, Timothy K.
Zhong, Chao
author_sort Cui, Mengkui
collection PubMed
description Engineering functional amyloids through a modular genetic strategy represents new opportunities for creating multifunctional molecular materials with tailored structures and performance. Despite important advances, how fusion modules affect the self-assembly and functional properties of amyloids remains elusive. Here, using Escherichia coli curli as a model system, we systematically studied the effect of flanking domains on the structures, assembly kinetics and functions of amyloids. The designed amyloids were composed of E. coli biofilm protein CsgA (as amyloidogenic cores) and one or two flanking domains, consisting of chitin-binding domains (CBDs) from Bacillus circulans chitinase, and/or mussel foot proteins (Mfps). Incorporation of fusion domains did not disrupt the typical β-sheet structures, but indeed affected assembly rate, morphology, and stiffness of resultant fibrils. Consequently, the CsgA-fusion fibrils, particularly those containing three domains, were much shorter than the CsgA-only fibrils. Furthermore, the stiffness of the resultant fibrils was heavily affected by the structural feature of fusion domains, with β-sheet-containing domains tending to increase the Young's modulus while random coil domains decreasing the Young's modulus. In addition, fibrils containing CBD domains showed higher chitin-binding activity compared to their CBD-free counterparts. The CBD-CsgA-Mfp3 construct exhibited significantly lower binding activity than Mfp5-CsgA-CBD due to inappropriate folding of the CBD domain in the former construct, in agreement with results based upon molecular dynamics modeling. Our study provides new insights into the assembly and functional properties of designer amyloid proteins with increasing complex domain structures and lays the foundation for the future design of functional amyloid-based structures and molecular materials.
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spelling pubmed-64611172019-04-23 Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties Cui, Mengkui Qi, Qi Gurry, Thomas Zhao, Tianxin An, Bolin Pu, Jiahua Gui, Xinrui Cheng, Allen A. Zhang, Siyu Xun, Dongmin Becce, Michele Briatico-Vangosa, Francesco Liu, Cong Lu, Timothy K. Zhong, Chao Chem Sci Chemistry Engineering functional amyloids through a modular genetic strategy represents new opportunities for creating multifunctional molecular materials with tailored structures and performance. Despite important advances, how fusion modules affect the self-assembly and functional properties of amyloids remains elusive. Here, using Escherichia coli curli as a model system, we systematically studied the effect of flanking domains on the structures, assembly kinetics and functions of amyloids. The designed amyloids were composed of E. coli biofilm protein CsgA (as amyloidogenic cores) and one or two flanking domains, consisting of chitin-binding domains (CBDs) from Bacillus circulans chitinase, and/or mussel foot proteins (Mfps). Incorporation of fusion domains did not disrupt the typical β-sheet structures, but indeed affected assembly rate, morphology, and stiffness of resultant fibrils. Consequently, the CsgA-fusion fibrils, particularly those containing three domains, were much shorter than the CsgA-only fibrils. Furthermore, the stiffness of the resultant fibrils was heavily affected by the structural feature of fusion domains, with β-sheet-containing domains tending to increase the Young's modulus while random coil domains decreasing the Young's modulus. In addition, fibrils containing CBD domains showed higher chitin-binding activity compared to their CBD-free counterparts. The CBD-CsgA-Mfp3 construct exhibited significantly lower binding activity than Mfp5-CsgA-CBD due to inappropriate folding of the CBD domain in the former construct, in agreement with results based upon molecular dynamics modeling. Our study provides new insights into the assembly and functional properties of designer amyloid proteins with increasing complex domain structures and lays the foundation for the future design of functional amyloid-based structures and molecular materials. Royal Society of Chemistry 2019-02-15 /pmc/articles/PMC6461117/ /pubmed/31015941 http://dx.doi.org/10.1039/c9sc00208a Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
Cui, Mengkui
Qi, Qi
Gurry, Thomas
Zhao, Tianxin
An, Bolin
Pu, Jiahua
Gui, Xinrui
Cheng, Allen A.
Zhang, Siyu
Xun, Dongmin
Becce, Michele
Briatico-Vangosa, Francesco
Liu, Cong
Lu, Timothy K.
Zhong, Chao
Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title_full Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title_fullStr Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title_full_unstemmed Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title_short Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
title_sort modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461117/
https://www.ncbi.nlm.nih.gov/pubmed/31015941
http://dx.doi.org/10.1039/c9sc00208a
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