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

doi:10.1039/c9sc00208a

	Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties
	Cui, Mengkui1,2,3 ; Qi, Qi1 ; Gurry, Thomas 4; Zhao, Tianxin1,2,3 ; An, Bolin1 ; Pu, Jiahua1 ; Gui, Xinrui 3,5; Cheng, Allen A.6; Zhang, Siyu1 ; Xun, Dongmin1 ; Becce, Michele 6,7,8; Briatico-Vangosa, Francesco 7; Liu, Cong 5; Lu, Timothy K.6; Zhong, Chao1
	2019-04-14
发表期刊	CHEMICAL SCIENCE (IF:7.6[JCR-2023],8.0[5-Year])
ISSN	2041-6520
卷号	10 期号:14 页码:4004-4014
发表状态	已发表
DOI	10.1039/c9sc00208a
摘要	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 -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 -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.
收录类别	EI ; SCIE ; SCI
语种	英语
资助项目	National Natural Science Foundation of China[U1532127] ; National Natural Science Foundation of China[31570972]
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:000467988600008
出版者	ROYAL SOC CHEMISTRY
EI入藏号	20191506765710
EI主题词	Bacteriology ; Chitin ; Elastic moduli ; Escherichia coli ; Glycoproteins ; Molecular dynamics ; Proteins ; Self assembly ; Stiffness
EI分类号	Structural Design, General:408.1 ; Biology:461.9 ; Physical Chemistry:801.4 ; Organic Compounds:804.1 ; Materials Science:951
WOS关键词	EXTRACELLULAR-MATRIX ; STRUCTURAL PREDICTIONS ; MECHANICAL-PROPERTIES ; FIBRILS ; A-BETA-42 ; DETERMINANTS ; BIOGENESIS ; ADHESIVES ; PROTEINS
原始文献类型	Article
引用统计	被引频次：19[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40852
专题	物质科学与技术学院_博士生物质科学与技术学院_PI研究组_钟超组物质科学与技术学院_硕士生物质科学与技术学院_本科生
通讯作者	Zhong, Chao
作者单位	1.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 200120, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China 4.MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA 5.Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 200032, Peoples R China 6.MIT, Dept Elect Engn & Comp Sci, Dept Biol Engn, Cambridge, MA 02139 USA 7.Politecn Milan, Dipartimento Chim Mat & Ingn Chim G Natta, Piazza Leonardo Vinci 32, I-20133 Milan, Italy 8.Imperial Coll London, Dept Mat, London SW7 2AZ, England
第一作者单位	物质科学与技术学院
通讯作者单位	物质科学与技术学院
第一作者的第一单位	物质科学与技术学院
推荐引用方式 GB/T 7714	Cui, Mengkui,Qi, Qi,Gurry, Thomas,et al. Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties[J]. CHEMICAL SCIENCE,2019,10(14):4004-4014.
APA	Cui, Mengkui.,Qi, Qi.,Gurry, Thomas.,Zhao, Tianxin.,An, Bolin.,...&Zhong, Chao.(2019).Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties.CHEMICAL SCIENCE,10(14),4004-4014.
MLA	Cui, Mengkui,et al."Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties".CHEMICAL SCIENCE 10.14(2019):4004-4014.