For Biophysics Week, members of the Early Careers Committee have written short summaries of classical biophysics studies, accessible to scientists and non-scientists alike.
This lay summary about the world's smallest rotary motor was written by Robert K. Nakamoto, University of Virginia.
A protein complex found throughout all the kingdoms of life is the FOF1 ATP synthase. As suggested by its name, it is an enzyme responsible for making most of a cell’s adenosine triphosphate, or ATP, the basic currency of energy for all organisms. With the major breakthrough from Sir John Walker at the Medical Research Council Laboratory in Cambridge, England, of solving the high-resolution protein structure of part of the ATP synthase complex (Abrahams et al. 1994), the field finally had evidence that the ATP synthase may be a rotary motor. This was an idea put forth by Paul Boyer at UCLA in the1980s based on his lifetime of studies to understand how the enzyme worked, and culminated in his model called the “binding change mechanism” (Boyer, 1989). Astonishingly, the structure showed that some of the components formed a donut-shaped ring like a pinwheel, and in the middle of the donut was a different protein that looked like an axle. An enzyme with such a rotational mechanism had never been described before and the race was on to experimentally prove it. Quickly, a couple of groups published papers using very sophisticated spectroscopic or biochemical approaches (Duncan et al. 1995, and Sabbert et al. 1996) to obtain results that were consistent with a rotary action, but were not without differing interpretations. In March 1997, Hiroyuji Noji, a graduate student at the time in the lab of Masasuke Yoshida, and working with Kazuhiko Kinoshita, a well-known single molecule biophysicist, reported an elegant method to observe the behavior of a single ATP synthase complex (Noji et al. 1997). They attached to the axle a filament of the protein actin that was long and could be seen in the microscope. When the ATP synthase was attached to a glass surface via the ring, the actin filament was observed whipping around like a whirligig when ATP was added. Incredibly, this tiny motor, 0.01 micron in diameter, could force rotation of filaments several microns in length. All one had to do was see the videos to be convinced that this enzyme worked as a rotary motor. In the fall of the same year, Paul Boyer and John Walker were awarded the Nobel Prize in Chemistry, which was shared with Jens Skou for his discovery of the sodium pump.
Abrahams, J. P. et al. (1994) "Structure at 2.8 Å resolution of F1-ATPase from bovine heart mitochondria." Nature 370: 621-628.
Boyer, P. D. (1989) "A perspective of the binding change mechanism for ATP synthesis." FASEB J. 3: 2164-2178.
Duncan, T. M. et al. (1995) "Rotation of subunits during catalysis by Escherichia coli F1-ATPase." Proc. Natl. Acad. Sci., U.S.A. 92: 10964-10968.
Sabbert, D. et al. (1996) "Intersubunit rotation in active F-ATPase." Nature 381: 623-625.
Noji, H. et al. (1997) "Direct observation of the rotation of F1-ATPase." Nature 386: 299-302.