Discovery and mechanism of a pH-dependent dual-binding-site switch in the interaction of a pair of protein modules

Xingzhe Yao; Chao Chen; Yefei Wang; Sheng Dong; Ya Jun Liu; Yifei Li; Zhenling Cui; Weibin Gong; Sarah Perrett; Lishan Yao; Raphael Lamed; Edward A. Bayer; Qiu Cui; Yingang Feng

doi:10.1126/sciadv.abd7182

Discovery and mechanism of a pH-dependent dual-binding-site switch in the interaction of a pair of protein modules

Xingzhe Yao, Chao Chen, Yefei Wang, Sheng Dong, Ya Jun Liu, Yifei Li, Zhenling Cui, Weibin Gong, Sarah Perrett, Lishan Yao, Raphael Lamed, Edward A. Bayer, Qiu Cui, Yingang Feng^*

^*Corresponding author for this work

Biotechnology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Many important proteins undergo pH-dependent conformational changes resulting in “on-off” switches for protein function, which are essential for regulation of life processes and have wide application potential. Here, we report a pair of cellulosomal assembly modules, comprising a cohesin and a dockerin from Clostridium acetobutylicum, which interact together following a unique pH-dependent switch between two functional sites rather than on-off states. The two cohesin-binding sites on the dockerin are switched from one to the other at pH 4.8 and 7.5 with a 180° rotation of the bound dockerin. Combined analysis by nuclear magnetic resonance spectroscopy, crystal structure determination, mutagenesis, and isothermal titration calorimetry elucidates the chemical and structural mechanism of the pH-dependent switching of the binding sites. The pH-dependent dual-binding-site switch not only represents an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials beyond an on-off switch for biotechnological applications.

Original language	English
Article number	abd7182
Journal	Science advances
Volume	6
Issue number	43
DOIs	https://doi.org/10.1126/sciadv.abd7182
State	Published - 23 Oct 2020

Funding

Funders	Funder number
National Natural Science Foundation of China	31800022, 31661143023, 31670735, 31700694, 31270784, 31570029, 31470747, 31872725
Chinese Academy of Sciences	XDA21060201
Israel Science Foundation	2566/16

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title = "Discovery and mechanism of a pH-dependent dual-binding-site switch in the interaction of a pair of protein modules",

abstract = "Many important proteins undergo pH-dependent conformational changes resulting in “on-off” switches for protein function, which are essential for regulation of life processes and have wide application potential. Here, we report a pair of cellulosomal assembly modules, comprising a cohesin and a dockerin from Clostridium acetobutylicum, which interact together following a unique pH-dependent switch between two functional sites rather than on-off states. The two cohesin-binding sites on the dockerin are switched from one to the other at pH 4.8 and 7.5 with a 180° rotation of the bound dockerin. Combined analysis by nuclear magnetic resonance spectroscopy, crystal structure determination, mutagenesis, and isothermal titration calorimetry elucidates the chemical and structural mechanism of the pH-dependent switching of the binding sites. The pH-dependent dual-binding-site switch not only represents an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials beyond an on-off switch for biotechnological applications.",

author = "Xingzhe Yao and Chao Chen and Yefei Wang and Sheng Dong and Liu, {Ya Jun} and Yifei Li and Zhenling Cui and Weibin Gong and Sarah Perrett and Lishan Yao and Raphael Lamed and Bayer, {Edward A.} and Qiu Cui and Yingang Feng",

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AU - Yao, Xingzhe

AU - Chen, Chao

AU - Wang, Yefei

AU - Dong, Sheng

AU - Liu, Ya Jun

AU - Li, Yifei

AU - Cui, Zhenling

AU - Gong, Weibin

AU - Perrett, Sarah

AU - Yao, Lishan

AU - Lamed, Raphael

AU - Bayer, Edward A.

AU - Cui, Qiu

AU - Feng, Yingang

N1 - Publisher Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2020/10/23

Y1 - 2020/10/23

N2 - Many important proteins undergo pH-dependent conformational changes resulting in “on-off” switches for protein function, which are essential for regulation of life processes and have wide application potential. Here, we report a pair of cellulosomal assembly modules, comprising a cohesin and a dockerin from Clostridium acetobutylicum, which interact together following a unique pH-dependent switch between two functional sites rather than on-off states. The two cohesin-binding sites on the dockerin are switched from one to the other at pH 4.8 and 7.5 with a 180° rotation of the bound dockerin. Combined analysis by nuclear magnetic resonance spectroscopy, crystal structure determination, mutagenesis, and isothermal titration calorimetry elucidates the chemical and structural mechanism of the pH-dependent switching of the binding sites. The pH-dependent dual-binding-site switch not only represents an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials beyond an on-off switch for biotechnological applications.

AB - Many important proteins undergo pH-dependent conformational changes resulting in “on-off” switches for protein function, which are essential for regulation of life processes and have wide application potential. Here, we report a pair of cellulosomal assembly modules, comprising a cohesin and a dockerin from Clostridium acetobutylicum, which interact together following a unique pH-dependent switch between two functional sites rather than on-off states. The two cohesin-binding sites on the dockerin are switched from one to the other at pH 4.8 and 7.5 with a 180° rotation of the bound dockerin. Combined analysis by nuclear magnetic resonance spectroscopy, crystal structure determination, mutagenesis, and isothermal titration calorimetry elucidates the chemical and structural mechanism of the pH-dependent switching of the binding sites. The pH-dependent dual-binding-site switch not only represents an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials beyond an on-off switch for biotechnological applications.

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Discovery and mechanism of a pH-dependent dual-binding-site switch in the interaction of a pair of protein modules

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