Directing curli polymerization with DNA origami nucleators

The physiological or pathological formation of fibrils often relies on molecular-scale nucleators that finely control the kinetics and structural features. However, mechanistic understanding of how protein nucleators mediate fibril formation in cells remains elusive. Here, we develop a CsgB-decorate...

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Main Authors: Mao, Xiuhai, Li, Ke, Liu, Mengmeng, Wang, Xinyu, Zhao, Tianxin, An, Bolin, Cui, Mengkui, Li, Yingfeng, Pu, Jiahua, Li, Jiang, Wang, Lihua, Lu, Timothy K, Fan, Chunhai, Zhong, Chao
Other Authors: Massachusetts Institute of Technology. Synthetic Biology Center
Format: Article
Language:English
Published: Nature Publishing Group 2019
Online Access:https://hdl.handle.net/1721.1/121274
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author Mao, Xiuhai
Li, Ke
Liu, Mengmeng
Wang, Xinyu
Zhao, Tianxin
An, Bolin
Cui, Mengkui
Li, Yingfeng
Pu, Jiahua
Li, Jiang
Wang, Lihua
Lu, Timothy K
Fan, Chunhai
Zhong, Chao
author2 Massachusetts Institute of Technology. Synthetic Biology Center
author_facet Massachusetts Institute of Technology. Synthetic Biology Center
Mao, Xiuhai
Li, Ke
Liu, Mengmeng
Wang, Xinyu
Zhao, Tianxin
An, Bolin
Cui, Mengkui
Li, Yingfeng
Pu, Jiahua
Li, Jiang
Wang, Lihua
Lu, Timothy K
Fan, Chunhai
Zhong, Chao
author_sort Mao, Xiuhai
collection MIT
description The physiological or pathological formation of fibrils often relies on molecular-scale nucleators that finely control the kinetics and structural features. However, mechanistic understanding of how protein nucleators mediate fibril formation in cells remains elusive. Here, we develop a CsgB-decorated DNA origami (CB-origami) to mimic protein nucleators in Escherichia coli biofilm that direct curli polymerization. We show that CB-origami directs curli subunit CsgA monomers to form oligomers and then accelerates fibril formation by increasing the proliferation rate of primary pathways. Fibrils grow either out from (departure mode) or towards the nucleators (arrival mode), implying two distinct roles of CsgB: as nucleation sites and as trap sites to capture growing nanofibrils in vicinity. Curli polymerization follows typical stop-and-go dynamics but exhibits a higher instantaneous elongation rate compared with independent fibril growth. This origami nucleator thus provides an in vitro platform for mechanistically probing molecular nucleation and controlling directional fibril polymerization for bionanotechnology.
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spelling mit-1721.1/1212742022-09-28T09:42:47Z Directing curli polymerization with DNA origami nucleators Mao, Xiuhai Li, Ke Liu, Mengmeng Wang, Xinyu Zhao, Tianxin An, Bolin Cui, Mengkui Li, Yingfeng Pu, Jiahua Li, Jiang Wang, Lihua Lu, Timothy K Fan, Chunhai Zhong, Chao Massachusetts Institute of Technology. Synthetic Biology Center Massachusetts Institute of Technology. Research Laboratory of Electronics The physiological or pathological formation of fibrils often relies on molecular-scale nucleators that finely control the kinetics and structural features. However, mechanistic understanding of how protein nucleators mediate fibril formation in cells remains elusive. Here, we develop a CsgB-decorated DNA origami (CB-origami) to mimic protein nucleators in Escherichia coli biofilm that direct curli polymerization. We show that CB-origami directs curli subunit CsgA monomers to form oligomers and then accelerates fibril formation by increasing the proliferation rate of primary pathways. Fibrils grow either out from (departure mode) or towards the nucleators (arrival mode), implying two distinct roles of CsgB: as nucleation sites and as trap sites to capture growing nanofibrils in vicinity. Curli polymerization follows typical stop-and-go dynamics but exhibits a higher instantaneous elongation rate compared with independent fibril growth. This origami nucleator thus provides an in vitro platform for mechanistically probing molecular nucleation and controlling directional fibril polymerization for bionanotechnology. 2019-06-13T21:42:12Z 2019-06-13T21:42:12Z 2019-03 2018-04 2019-06-13T14:08:50Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 https://hdl.handle.net/1721.1/121274 Mao, Xiuhai et al. "Directing curli polymerization with DNA origami nucleators." Nature Communications 10 (March 2019): 1395 © 2019 The Author(s) en http://dx.doi.org/10.1038/s41467-019-09369-6 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle Mao, Xiuhai
Li, Ke
Liu, Mengmeng
Wang, Xinyu
Zhao, Tianxin
An, Bolin
Cui, Mengkui
Li, Yingfeng
Pu, Jiahua
Li, Jiang
Wang, Lihua
Lu, Timothy K
Fan, Chunhai
Zhong, Chao
Directing curli polymerization with DNA origami nucleators
title Directing curli polymerization with DNA origami nucleators
title_full Directing curli polymerization with DNA origami nucleators
title_fullStr Directing curli polymerization with DNA origami nucleators
title_full_unstemmed Directing curli polymerization with DNA origami nucleators
title_short Directing curli polymerization with DNA origami nucleators
title_sort directing curli polymerization with dna origami nucleators
url https://hdl.handle.net/1721.1/121274
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