Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Revealing the inner workings of a molecular motor

12.01.2015

In research published in the Journal of Cell Biology, scientists from the RIKEN Brain Science Institute in Japan have made important steps toward understanding how dynein--a "molecular motor"--walks along tube-like structures in the cell to move cellular cargo from the outer structures toward the cell body of neurons. The action of this molecule is important for a number of cell functions including axonal transport and chromosome segregation, and its dysfunction is known to lead to a congenital developmental brain disorder known as lissencephaly.

Though cells may look like shapeless blobs of liquid encased in a membrane, in fact they have a complex skeleton-like structure, known as the cytoskeleton, made up of filaments called microtubules. Motor proteins, which include dynein and kinesin, can move along these tubules to transport cargo into and out of the center of the cell.


Schematic representation of the dynein-microtubule complex showing the structural elements likely to be involved in allosteric communication between the microtubule and the ATPase site in dynein

The motor proteins use an energy-currency molecule, ATP, to power their movements along the microtubules. The motor proteins hydrolyze ATP to ADP, and convert the released chemical energy to mechanical energy which is used for movement. The mechanism is quite well understood for kinesin, but in the case of dynein, it has been difficult to explain how communication takes place between the site of microtubule binding and the site of ATP hydrolysis, which are relatively far from each other, separated by a stalk.

In the new research, performed in collaboration with several other institutes including the University of Osaka, Waseda, and Hosei University, the RIKEN scientists used cryo electron microscopy--where molecules are cooled to very low temperatures in the microscope--and examined the structure of dynein on the microtubule.

They showed that two specific amino acid residues on the microtubule structure, R403 and E416, are key to turning on the switch that is critical for the activation of the dynein motor--demonstrating that when mutations in these sequences are present, the dynein fails to achieve directional movement on the microtubule, ending up simply moving back and forth in a random fashion.

This lends weight to the idea, that has been generally accepted, that the motion of molecular motors is basically driven by random, Brownian motion, and that motors are able to move in one direction thanks to subtle changes in the strength of bonds at the motor-microtubule interface.

Additionally, the group discovered that turning on the mechanical switch at the motor-microtubule interface leads to ATP hydrolysis. Their results altogether indicate that the subtle structural changes in the bonds at the interface are transmitted through a small change in the structure of the stalk--there are two coils that link the two binding regions, and a small shift in the configuration of the coils gives the cue for ATP hydrolysis at the ATP binding site.

Seiichi Uchimura, the first author of the paper, said, "We were able to clearly demonstrate that the dynein molecular motor is activated by a 'switch' that controls mutual interactions between dynein and the microtubule. This is important, as a mutation in the structure of the switch has been demonstrated to cause lissencephaly, a congenital disorder."

According to Etsuko Muto, who led the research team, "In the future, we hope that further understanding the interplay between dynein and microtubule, as this could pave the way for therapies for these conditions."

Media Contact

Jens Wilkinson
jens.wilkinson@riken.jp
81-048-462-1225

 @riken_en

http://www.riken.jp/en/

Jens Wilkinson | EurekAlert!

Further reports about: RIKEN Uchimura activation dynein hydrolysis kinesin microtubule microtubules molecular motor proteins

More articles from Life Sciences:

nachricht Channels for the Supply of Energy
19.11.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Vine Compound Starves Cancer Cells
19.11.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

How Humans and Machines Navigate Complex Situations

19.11.2018 | Science Education

Finding plastic litter from afar

19.11.2018 | Ecology, The Environment and Conservation

Channels for the Supply of Energy

19.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>