Re-engineering of protein motors to understand mechanisms biasing random motion and generating collective dynamics
Graphical abstract
Introduction
Since the Industrial Revolution, a variety of machines based on top-down control systems have been made and prevailed in the world. However, these traditional machines, including engines, robots, computers and their networks are showing weaknesses such as difficulty adapting to dramatic changes in the environment. As alternative strategies, increasing attention has been focused on the bottom-up strategies that life adopts.
Section snippets
Autonomous molecular motors that life uses
In living organisms, systems at all levels naturally perform incredibly advanced distributed processing, from the level of ant societies, to individuals, tissues, and down to the cellular level. At the cellular level, the motile machineries such as muscle, mitotic spindle, and cilia/flagella use nanometre-scale molecular machines made of proteins, called biological molecular motors (biomolecular motors), which move along cytoskeletal tracks. These motors capture ATP molecules dissolved in
Key questions in the biomolecular motor field
Remarkably, these tiny machines directly convert chemical energy into directional movement, which makes these motors distinct from man-made macroscopic machines and potentially useful as nanometre-sized actuators [8, 9••]. However, the essential mechanisms that enable such a difficult task is currently unknown. The problem is that biomolecular motors are working in a stochastic environment where the energy of thermal fluctuations is comparable to the energy that can be obtained from ATP
Constructive (synthetic) approaches to biomolecular motors
One effective way to overcome this problem is to take a constructive (or synthetic) approach [11]. The basic idea of the approach is to design (or re-design) and construct new biological components and systems in order to understand life processes. In the case of biomolecular motors, one strategy would be to construct a molecular machine that captures the essence of biomolecular motors. By constructing diverse motile machines that correspond to a single function of directional motility and
Constructing de novo motors
Construction of de novo molecular machines has become a major theme in nanomachine engineering and synthetic biology. In chemistry, three researchers have developed extremely small molecular machines, inspired by biomolecular machines that drive the processes of life. The 2016 Nobel Prize in Chemistry was awarded for their research implementing nanometre scale switches and motors. Switches and motors are similar in that they change their state in response to the environment, but motors
Increasing levels of complexity
Collective behaviour emerging from multi-motor assemblies should be an important step toward understanding the mechanisms generating macroscopic dynamics. A pioneering work [36] engaged many kinesin motors to artificial protein scaffolds with defined motor–motor spacing, and demonstrated that cooperativity among motors can emerge as enhanced ATPase activity and motility. For studying such collective behaviour, the use of DNA-based scaffolds has become more common since the late 2000s. DNA
Toward macroscopic control
In vivo, it is well established that motors and cytoskeletal tracks undergo spontaneous self-assembly into defined structures with surprising accuracy. Yet, a significant knowledge gap exists between the properties of individual molecules and their collective behaviour, which limits our ability to fabricate smart molecules that self-assemble to perform desired functions. To fill this gap, considerable progress has been made through a combination of experimental and theoretical studies [47, 48,
Conclusions
We propose that re-engineering of biomolecular motors might enable us to understand the mechanisms of individual motors and their self-organization. Several hierarchical levels of complexity exist; individual motors themselves consist of polymers that possess numerous internal degrees of freedom, making it difficult to predict the functions from the amino acid sequences. Likewise, networks of molecular motors and cytoskeleton contain complexity with multiple levels of hierarchy that interact
Conflict of interest statement
The authors declare no competing financial interests.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
K. Furuta is supported in part by a Grant-in-Aid for Scientific Research C from the Japan Society for the Promotion of Science (grant number 15KT0155 to K.F.).
References (59)
The molecular motor toolbox for intracellular transport
Cell
(2003)- et al.
Rotary ATPases — dynamic molecular machines
Curr Opin Struct Biol
(2014) - et al.
Exploiting molecular motors as nanomachines: the mechanisms of de novo and re-engineered cytoskeletal motors
Curr Opin Biotechnol
(2017) - et al.
Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines
Nature
(2005) - et al.
Strain through the neck linker ensures processive runs: a DNA-kinesin hybrid nanomachine study
EMBO J
(2010) - et al.
Structural basis of backwards motion in kinesin-1-kinesin-14 chimera: implication for kinesin-14 motility
Structure
(2016) - et al.
Molecular engineering of a backwards-moving myosin motor
Nature
(2004) - et al.
A cargo-sorting DNA robot
Science
(2017) - et al.
Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments
Nat Nanotechnol
(2015) - et al.
Polar patterns of driven filaments
Nature
(2010)
Phototaxis of synthetic microswimmers in optical landscapes
Nat Commun
Direct observation of base-pair stepping by RNA polymerase
Nature
AAA+ proteases: ATP-fueled machines of protein destruction
Annu Rev Biochem
Direct measurement of the mechanical work during translocation by the ribosome
Elife
Tubulin depolymerization may be an ancient biological motor
J Cell Sci
The biophysicist's guide to the bacterial flagellar motor
Adv Phys: X
Biomolecular motors operating in engineered environments
Protein Sci Encycl
Toward the Design Principles of Molecular Machines
Constructive complexity and artificial reality: an introduction
Phys D: Nonlinear Phenom
The affinity of the dynein microtubule-binding domain is modulated by the conformation of its coiled-coil stalk
J Biol Chem
Engineering the processive run length of the kinesin motor
J Cell Biol
Reversal in the direction of movement of a molecular motor
Nature
Determinants of kinesin motor polarity
Science
The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain
Cell
The power stroke of myosin VI and the basis of reverse directionality
Proc Natl Acad Sci U S A
Engineering controllable bidirectional molecular motors based on myosin
Nat Nanotechnol
Remote control of myosin and kinesin motors using light-activated gearshifting
Nat Nanotechnol
Controllable molecular motors engineered from myosin and RNA
Nat Nanotechnol
Structure and functional role of dynein's microtubule-binding domain
Science
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