Originally Published MDDI April 2004
|A backward-moving myosin was made from three molecular building blocks.|
New research has shown that mechano-enzymes called myosins can be made to move in a reverse direction. This discovery could make building future nanotechnology-based medical devices less complicated than previously thought.
The new study comes from the Hannover Medical School (Hannover, Germany) and the Max Planck Institute for Medical Research (Heidelberg, Germany). It describes how the team was able to engineer a backward-moving myosin from three molecular building blocks. Full details appear in the February 5, 2004, edition of Nature.
“Being able to change the activity of a mechano-enzyme in a specific way with a predictable outcome has implications for the development of medical applications and nanoscale analytical devices,” said lead researcher Dietmar J. Manstein, PhD, a professor of biophysical chemistry at Hannover Medical School. “It is now trivial to combine these motors with further building blocks that, for example, target them to specific locations or mutate them in a way such that their activity can be triggered by light of a specific wavelength.”
Myosins contain a common motor domain. They use it to convert energy into movement, exerted against polar actin filaments. The first block for the backward-moving myosin is a forward-moving one. The others are a directional inverter and an artificial lever arm. Rotating the movement of the lever arm 180o can achieve
reverse-direction movement. “The work is based on a very simple idea,” Manstein said. “The translational movement of the tip of a lever depends on the angle of rotation and the direction in which the lever projects away from the axis of rotation. The difficult part was to rotate the direction of the lever arm in precisely the right orientation without creating sterical clashes between domains and compromising the stiffness of the domains and the joints between them.”
These findings could lead to more research on how to derive applications from engineering proteins from known building blocks that are biologically unrelated. “Currently we are combining fluorescent probe techniques with the engineered attachment of long amplifier elements to study the conformational dynamics of enzymes with high spatial and temporal resolution,” said Georgios Tsiavaliaris, PhD, another professor of biophysical chemistry at Hannover Medical School.
Particularly notable, said Manstein, is that “we had to reach only once into the toolbox of molecular building blocks to produce a protein with the predicted activity.” That saved a lot of time compared to a trial-and-error approach.
Joining Manstein and Tsiavaliaris on the project was Setsuko Fujita-Becker, PhD, a professor of biophysics at the Max Planck Institute. Funding for their research came from a molecular motors project grant from Deutche Forschungsgemeinschaft.
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