Walk This Way: Scientists and MBL Physiology Course Students Describe How a Motor Protein “Steps Out”

Just like people, some proteins have characteristic ways of “walking,” which (also like human gaits) are not so easy to describe. But now scientists have discovered the unique “drunken sailor” gait of dynein, a protein that is critical for the function of every cell in the body and whose malfunction has been associated with neurodegenerative disorders such as Lou Gehrig’s disease and Parkinson’s disease.

The research, which was led by Samara Reck-Peterson of Harvard Medical School and partially conducted in the MBL Physiology Course, received advance online publication this week in the journal Nature Structural & Molecular Biology.

Found in all of our cells, dynein is one of three types of “motor proteins”: tiny molecular machines that are constantly working to shuttle materials needed to keep cells alive, allow cells to move and divide, and talk to their neighbors. All three types of motor protein (dynein, myosin, and kinesin) are “two-footed” and use the energy from breaking chemical bonds to generate movement.

“The myosin and kinesin motors work by walking more or less like we do: one foot in front of the other in a straight line,” says Reck-Peterson. “We have discovered that the third motor model, dynein, appears to be different. Its two feet are at times uncoordinated and often veer from side to side (think drunken sailor). This mode of walking makes the dynein motor unique and may allow it to navigate obstacles while performing its transport functions in cells. Interestingly, our data also suggest that the dynein motor becomes more coordinated when it is hauling something large, implying that the motor can become more efficient when necessary.”

Co-authors Elizabeth Villa of the Max Planck Institute of Biochemistry and David Wu of UCLA’s Geffen School of Medicine were students in the 2007 MBL Physiology Course. There, they began writing custom software code to analyze molecular movement by “two-dimensional particle tracking,” which was used in this research.

Athough this discovery is but a “first step,” deciphering the walking mechanism of dynein may one day shed light on the molecular basis of neurodegenerative disease, Reck-Peterson says.

Dynein can step sideways, forward, backward, take big and little steps. This is in real contrast to other molecular motors. It may even be able to step around any number of cellular obstacles. Top panel: each fluorescently labeled “leg” of dynein is represented by a red or blue dot. The gray “highway” is the cellular filament (microtubule) on which dynein moves. Bottom panel: In contrast to dynein, other motors, such as kinesin, step much more regularly. Animations by Janet Iwasa, courtesy Harvard Medical School. Neuroscience video from HarvardMedicalSchool user on YouTube.com.

Molecular motors, built from proteins, are a kind of transport service that keep us functioning by trafficking essential chemical packages throughout the cell. To understand how molecular motors work, some researchers are creating animations. Here, each “leg” of a molecular motor called dynein moves as it progresses along a cellular structure called a microtubule. New data suggest that dynein’s walk is even stranger than the one modeled. Neuroscience video from HarvardMedicalSchool user on YouTube.com.

Notes about this physiology research article

Contact: Diana Kenney – Marine Biological Laboratory
Source: Marine Biological Laboratory press release
Original Research: Qiu W., Derr ND, Goodman BS, Villa E, Wu D, Shih W, and Reck-Peterson SL (2012) “Dynein achieves processive motion using both stochastic and coordinated stepping.” Nature Struct. & Mol. Biol. research abstract
Video Source: Neuroscience videos from YouTube user HarvardMedicalSchool
Image Source: Image adapted from video uploaded to Youtube.com by HarvardMedicalSchool

Animated still showing what looks like a pair of legs walking on a log. Digital representation of dynein stepping process.
To understand how molecular motors work, some researchers are creating animations. Here, each “leg” of a molecular motor called dynein moves as it progresses along a cellular structure called a microtubule. Image from HarvardMedicalSchool video on Youtube.
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