Modular Genetic Design of Multi-domain Functional Amyloids: Insights into Self-assembly and Functional Properties
Name
c9sc00208a.pdf
Description
Published version
Size
1.79 MB
Format
Adobe PDF
Checksum (MD5)
15a83e42b20d606d471d377a6532b7d8
Author(s)
Cui, Mengkui
Qi, Qi
Gurry, Thomas
Zhao, Tianxin
An, Bolin
Pu, Jiahua
Gui, Xinrui
Cheng, Allen A
Zhang, Siyu
Xun, Dongmin
Date Issued
2019
Journal
Chemical Science
Publisher
Royal Society of Chemistry (RSC)
Version
Final published version
Abstract
© The Royal Society of 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution Noncommercial 3.0 unported license
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DOI of Published Version
https://doi.org/10.1039/C9SC00208A
