Biohistory journal, Winter, 2004
Research: Index > Research of rotating molecule, ATP synthetase
Research
Narrative science
Research of rotating molecule, ATP synthetase
Hiroyuki Noji,
University of Tokyo Institute of Industrial Science


Crystal structure of F1 motor
(side view)
    The energy required by living creatures is transported in the form of ATP (adenosine triphosphate). The ATP synthesizing enzyme is the world's smallest rotating motor, and it efficiently creates ATP. It is located in cellular membranes and the mitochondria endomembrane. It is the combination of two rotating motors (the F1 and F0) that are about 10 nm in diameter and height and are easily separated. The F0 rotates by utilizing the difference in the hydrogen ion concentrations on both sides of the biological membranes. ATP is synthesized from the ADP and phosphoric acid.
    When there is a slight difference in the concentration of hydrogen ions, the F1 breaks up the ATP into ADP and phosphoric acid. The energy obtained rotates the F0 in the opposite direction and transports the hydrogen ions. Thus, the ATP synthesizing enzyme is an extremely interesting molecular machine that converts the electrochemical potential of the hydrogen ion and ATP by a rotating movement. It has been rotating within the organism for at least two billion years. We observed the movement of the single motor - in other words, the single molecule (the easily handled F1 motor) to look for the mechanism by which this small, delicate molecular motor works.

 The method for manipulating the molecule
    The ATP synthesizing enzyme is extremely small and difficult to observe. The rotation was observed by angling the rotor of the F1 motor fixed to glass and installing magnetic beads. This also enabled the manipulation of the molecule's direction using an electromagnet to provide an external magnetic field.
Rotating magnetic beads under the microscope
( QuickTime/3.6MB)

 Looking at the molecule
An enlargement
    We made an unexpected discovery when observing the movement of the F1 molecule. For example, during the F1's rotation, the rotation is sometimes suspended and the molecule briefly idles (rotational Brownian motion). Rotation resumes about 30 seconds later. Unless the ADP resulting from the decomposition of the ATP is separated, the next ATP decomposition reaction will not begin and rotation will stop. Pressing the F1 that seems to be lagging in the direction of rotation will cause rotation to resume immediately. If it is pressed in the opposite direction, however, it will briefly remain motionless. The ADP affinity weakens in the direction of rotation and strengthens in the opposite direction (the direction of ATP synthesis).
    This is a superb mechanism in which the ATP breakup and synthesis are both accomplished with a single motor. Stopping the lagging F1 at the idling center of rotation prevents rotation from resuming. If it happens to be jolted in the direction of rotation while idling, the ADP would be separated and rotation would likely resume.

    The molecule is addressed by operating a single molecule, and its behavior is carefully observed. The reaction is different for each molecule. This tests the abilities of the scientist, who must determine how to organize this for science, which demands repeatability. This may well create a narration for science in the future.

Hiroyuki Noji
Awarded a doctorate degree in 1997 after completing the doctorate course of the Tokyo Institute of Technology's Interdisciplinary Graduate School of Science and Engineering. After serving as a postdoctoral fellow at the Japan Science and Technology Agency and a researcher in the Sakigake 21 program "Organization and Function", he was named associate professor at the University of Tokyo Institute of Industrial Science, a position he holds today.
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