For the first time, scientists can glimpse the priming stroke of the dynein motor protein with atomic-scale detail and real-time resolution. Associate Professor Mert Gur and his team have published a new article, “The Mechanism and Energetics of the Dynein Protein Stroke,” in collaboration with the Yildiz lab at the University of California, Berkeley.  

“Dyneins are tiny engines inside the cell, which move things around inside the cell,” Gur said. “They bring things where they need to go.” 

These tiny engines play a key role in transport within the cell and cell division. Dyneins also have the potential to be future drug targets for diseases like cancer.  

“In cancer, you have uncontrolled cell division, but it’s with cells that aren’t healthy,” Gur said. “Now, we know that dyneins are important for cell division. To a degree, if you can inhibit cancer cells from doing their function, this can prevent cell proliferation and the spread of cancer.” 

Prior to this study, limitations in experimental methods and computational resources prevented researchers from visualizing the dynein power cycle with atomic-scale detail. Dyneins are very large proteins, which makes it challenging to view their complete atomic structures.  

Gur and his team used all-atom molecular dynamic (MD) simulations, which provide high-definition movies of dyneins, to get an inside look at the priming stroke of this cycle. With MD simulations, researchers can view dyneins with femtosecond resolution. The ratio of one femtosecond to one second is equivalent to that of one second to 31.7 million years. This is a scale small enough to see atoms “wiggle.”

“This is the era where we’re able to do amazing things with technology,” said Gur. “We are now able to predict how a protein would move in a specific environment.” 

Using the advanced technology of MD simulations, Gur recorded the priming stroke of the dynein power cycle. The dynein power cycle has two strokes: a priming stroke and a power stroke. To visualize this cycle, Gur compares dyneins to the movement of legs. 

“Two dyneins would be working together,” he said. “In order to go forward, you lift one of the legs up and then you swing it. The forward swinging motion, or the priming stroke, is what brings you forward.” 

During the power stroke, dyneins perform work to pull cargo forward, similar to how a grounded leg performs a push and enables us to move.  

Now that he has analyzed the priming stroke, Gur and his team are eager to continue their research on dyneins.  

“We have half of the mechanical cycle now,” he said. “The other part is to investigate how to regulate dynein function with molecules.”