8/14/2019 Protonic NanoMachine

1/3

Protonic NanoMachine

The theme of the project

The origin of such various life functions as energymetabolism, material metabolism, self-multiplication andenvironmental adaptability is the flow of energy, signal and materialthrough the complex networks formed by macromolecules such asproteins and nucleic acids. An enormous number of thosemacromolecules play each role just like purposefully designedmachines and maintain the complex network activities. They could becalled molecular machine, but they have characteristics quitedifferent from human-made ones in the following aspects:

(1) Designed with individual atoms as functional parts andtherefore of nanometer size.

(2) Self-organize the structure at the right time and place in thecellular organization.

(3) Have flexibility and adaptability because of weakinteractions of hydrogen bonding that forms the structure.

The proton (H+) plays important roles in these functions andmechanisms, in a similar way to what electrons do in semiconductordevices. In the activities of living cells, where the water solution is thebasic medium for all the reactions, protons are the carriers of the

signal and energy. Therefore, it is essential to clarify the mechanismsof macromolecular functions based on the behaviors of protonmovements in order to understand the activities of life at molecularlevel.

The aim of this project is to try to understand the physicalprocesses and mechanisms unique to biological molecular machines,which efficiently transmit, amplify and transform extremely fineenergy and signal of conformational changes through protonexchange. The research effort will be concentrated on the atomicresolution structure analysis of macromolecular complexes by X-raydiffraction and electron microscopy and the analysis of energytransduction dynamics of the systems by measuring their sub-nanoscale movements and proton flows that are close to the presentlimit of experimental detection. The results are expected to produceimportant clues to the unknown principle of the macromolecularmachinery.

The methods of structure and functional analyses ofmacromolecular complexes developed by these studies will beapplicable to many other systems of important functions for better

understandings of the mechanisms and would make a greatcontribution to medical applications as well. These studies are alsoexpected to give us some clues to the development of a novel energy

8/14/2019 Protonic NanoMachine

2/3

conversion technology that is as efficient and well regulated as thebiological system.

We chose the bacterial flagellum as the target system of ourresearch project. The bacterial flagellum is composed of a switchablerotary motor, a universal joint and a helical propeller, all of which arebuilt by self-assembly of specifically designed component proteins. The motor is powered by the proton motive force, just as

F1F0ATPsynthase. The component proteins are exported from thecytoplasmic side to the distal end of the structure under constructionthrough its narrow central channel by the export apparatus located atthe base of the flagellum. The assembly occurs at the distal end,where a capping complex helps its efficient assembly process. All ofthese functions are supported by mechanisms that are not yet known.But, one thing is at least clear that we must see the atomicarrangements and the dynamics of this huge molecular assembly tounderstand how these intricate and dynamic functions are exhibited.

Groups of the project includes:

(1) NanoAssembly: will study the regulation mechanisms ofmacromolecular assemblies by X-ray crystallography and fiberdiffraction.

(2) NanoSwitching: will approach the switching mechanisms ofmacromolecular assemblies by electron cryomicroscopy and imageanalysis.

8/14/2019 Protonic NanoMachine

3/3