|NATIONAL INSTITUTES OF HEALTH||
National Institute of Arthritis and Musculoskeletal and Skin Diseases
|Embargoed for release
Wednesday, April 10, 1996
4 p.m. Eastern Time
Contact: Elia Ben-Arii
Researchers supported by the National Institutes of Health (NIH) studying the three-dimensional crystal structure of molecular motor proteins of the kinesin family have reported the unexpected finding that the same basic motor design is used to drive muscle contraction and cell division. The finding was a surprise because these processes are driven by motor proteins that differ radically in size and amino acid sequence and interact with distinct protein cofactors.
Molecular motor proteins harness chemical energy to generate motion the way an engine uses gasoline to make a car move. The chemical fuel that these molecular motors burn to produce mechanical power is adenosine triphosphate (ATP), which is produced when the body metabolizes the food we eat.
These results are reported in the April 11, 1996 issue of Nature by Dr. Ronald D. Vale, Dr. Robert J. Fletterick and their colleagues at the University of California, San Francisco (UCSF). Dr. Vale is in the Howard Hughes Medical Institute at UCSF.
Kinesins are molecular motors that move chromosomes into the two "daughter cells" during cell division; transport nutrients along the long, thin fibers of nerve cells; and shuttle organelles within cells. Members of the kinesin family interact with protein polymers called microtubules, which serve as tracks along which kinesins transport their loads. Myosin drives muscle contraction, converting chemical energy into force through its interaction with filaments made from the protein actin.
Until now, researchers had no hint that the structures of the motor regions of myosin and kinesin, members of two of the three distinct families of molecular motors, would be so similar. The amino acid sequences of the two proteins are not related, and the size of the myosin motor region is more than double that of kinesin, which is the smallest known molecular motor. In addition, the shapes of the two motor regions did not look similar when viewed by electron microscopy.
The new research shows that the more detailed three-dimensional atomic structure of the active motor region of kinesin is strikingly similar to that of the myosin active region. These similarities were revealed by examining the three-dimensional structure of kinesin using x-ray crystallography, which provides about ten times stronger magnification than electron microscopy, and comparing it to the known three-dimensional crystal structure of myosin, which was reported by NIH-supported researchers in 1993.
In an accompanying paper, the investigators show that the three-dimensional structure of the motor region of NCD, a member of the kinesin family, is very similar to that of kinesin though it moves in the reverse direction. They also found strong similarities in structure and amino acid sequence between several small regions in the motor proteins and the "switch" regions of a family of proteins called G proteins. G proteins are molecules that help transmit various types of biochemical signals within cells. The similarities between the motor proteins and the switch regions of G proteins suggest that the same mechanism may be used to switch these proteins on and off.
The structural similarities between myosin and the two kinesin family members, kinesin and NCD, suggest that both families of motor proteins use a similar force-generating strategy. In addition, the researchers say, these results suggest that the myosin and kinesin families of motor proteins may have evolved from a common protein ancestor.
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This research was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); the National Heart, Lung, and Blood Institute; and the National Institute of General Medical Sciences, components of the National Institutes of Health.
For names of experts who can comment on this research, please contact Elia Ben-Ari, NIAMS Office of Scientific and Health Communications, at (301) 496-8190
F. J. Kull, E. P. Sablin, R. Lau, R. J. Fletterick, and R. D. Vale. Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature1996; 380:550-555.
E. P. Sablin, F. J. Kull, R. Cooke, R. D. Vale, and R. J. Fletterick. Crystal structure of the motor domain of the kinesin-related motor NCD. Nature 1996; 380:555-559.