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Synthetic biology approaches to dissecting linear motor protein function : towards the design and synthesis of artificial autonomous protein walkers

Linke, Heiner LU ; Höcker, Birte ; Furuta, Ken’ya ; Forde, Nancy R. and Curmi, Paul M.G. (2020) In Biophysical Reviews 12(4). p.1041-1054
Abstract

Molecular motors and machines are essential for all cellular processes that together enable life. Built from proteins with a wide range of properties, functionalities and performance characteristics, biological motors perform complex tasks and can transduce chemical energy into mechanical work more efficiently than human-made combustion engines. Sophisticated studies of biological protein motors have provided many structural and biophysical insights and enabled the development of models for motor function. However, from the study of highly evolved, biological motors, it remains difficult to discern detailed mechanisms, for example, about the relative role of different force generation mechanisms, or how information is communicated... (More)

Molecular motors and machines are essential for all cellular processes that together enable life. Built from proteins with a wide range of properties, functionalities and performance characteristics, biological motors perform complex tasks and can transduce chemical energy into mechanical work more efficiently than human-made combustion engines. Sophisticated studies of biological protein motors have provided many structural and biophysical insights and enabled the development of models for motor function. However, from the study of highly evolved, biological motors, it remains difficult to discern detailed mechanisms, for example, about the relative role of different force generation mechanisms, or how information is communicated across a protein to achieve the necessary coordination. A promising, complementary approach to answering these questions is to build synthetic protein motors from the bottom up. Indeed, much effort has been invested in functional protein design, but so far, the “holy grail” of designing and building a functional synthetic protein motor has not been realized. Here, we review the progress made to date, and we put forward a roadmap for achieving the aim of constructing the first artificial, autonomously running protein motor. Specifically, we propose to break down the task into (i) enzymatic control of track binding, (ii) the engineering of asymmetry and (iii) the engineering of allosteric control for internal communication. We also propose specific approaches for solving each of these challenges.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Allostery, Energy transduction, Motor protein, Processivity, Synthetic biology, Thermal fluctuations
in
Biophysical Reviews
volume
12
issue
4
pages
14 pages
publisher
Springer
external identifiers
  • scopus:85087810850
  • pmid:32651904
ISSN
1867-2450
DOI
10.1007/s12551-020-00717-1
language
English
LU publication?
yes
id
9ce7f9ad-6ae8-43cd-a67f-895447c084b6
date added to LUP
2020-07-23 12:49:19
date last changed
2021-02-23 01:05:16
@article{9ce7f9ad-6ae8-43cd-a67f-895447c084b6,
  abstract     = {<p>Molecular motors and machines are essential for all cellular processes that together enable life. Built from proteins with a wide range of properties, functionalities and performance characteristics, biological motors perform complex tasks and can transduce chemical energy into mechanical work more efficiently than human-made combustion engines. Sophisticated studies of biological protein motors have provided many structural and biophysical insights and enabled the development of models for motor function. However, from the study of highly evolved, biological motors, it remains difficult to discern detailed mechanisms, for example, about the relative role of different force generation mechanisms, or how information is communicated across a protein to achieve the necessary coordination. A promising, complementary approach to answering these questions is to build synthetic protein motors from the bottom up. Indeed, much effort has been invested in functional protein design, but so far, the “holy grail” of designing and building a functional synthetic protein motor has not been realized. Here, we review the progress made to date, and we put forward a roadmap for achieving the aim of constructing the first artificial, autonomously running protein motor. Specifically, we propose to break down the task into (i) enzymatic control of track binding, (ii) the engineering of asymmetry and (iii) the engineering of allosteric control for internal communication. We also propose specific approaches for solving each of these challenges.</p>},
  author       = {Linke, Heiner and Höcker, Birte and Furuta, Ken’ya and Forde, Nancy R. and Curmi, Paul M.G.},
  issn         = {1867-2450},
  language     = {eng},
  number       = {4},
  pages        = {1041--1054},
  publisher    = {Springer},
  series       = {Biophysical Reviews},
  title        = {Synthetic biology approaches to dissecting linear motor protein function : towards the design and synthesis of artificial autonomous protein walkers},
  url          = {http://dx.doi.org/10.1007/s12551-020-00717-1},
  doi          = {10.1007/s12551-020-00717-1},
  volume       = {12},
  year         = {2020},
}