Scientists reveal structural secrets of nature’s little locomotive

A team led by scientists at The Scripps Research Institute (TSRI) has determined the basic structural organization of a molecular motor that hauls cargoes and performs other critical functions within cells.    

Biologists have long wanted to know how this molecular motor—called the “dynein-dynactin complex"—works. But the complex’s large size, myriad subunits and high flexibility have until now restricted structural studies to small pieces of the whole.

In the new research, however, TSRI biologist Gabriel C. Lander and his laboratory, in collaboration with Trina A. Schroer and her group at Johns Hopkins University, created a picture of the whole dynein-dynactin structure.

"This work gives us critical insights into the regulation of the dynein motor and establishes a structural framework for understanding why defects in this system have been linked to diseases such as Huntington’s, Parkinson’s, and Alzheimer’s,” said Lander.

The findings are reported in a Nature Structural & Molecular Biology advance online publication on March 9, 2015.

Credit: Lander lab, The Scripps Research Institute.      

Revealing the Inner Workings of a Molecular Motor

Read the full article Revealing the Inner Workings of a Molecular Motor at NeuroscienceNews.com.

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 research in in Journal of Cell Biology. (full access paywall)

Research: “A flipped ion pair at the dynein–microtubule interface is critical for dynein motility and ATPase activation” by Seiichi Uchimura, Takashi Fujii, Hiroko Takazaki, Rie Ayukawa, Yosuke Nishikawa, Itsushi Minoura, You Hachikubo, Genji Kurisu, Kazuo Sutoh, Takahide Kon, Keiichi Namba, and Etsuko Muto in Journal of Cell Biology. doi:10.1083/jcb.201407039 (http://dx.doi.org/10.1083/jcb.201407039)

Image: 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. Image adapted from the RIKEN press release.

Intracellular cargo is transported by multiple motor proteins. Because of the force balance of motors with mixed polarities, cargo moves bidirectionally to achieve biological functions. Here, we propose a microtubule gliding assay for a tug-of-war study of kinesin and dynein. A boundary of the two motor groups is created by photolithographically patterning gold to selectively attach kinesin to the glass and dynein to the gold surface using a self-assembled monolayer. The relationship between the ratio of two antagonistic motor numbers and the velocity is derived from a force-velocity relationship for each motor to calculate the detachment force and motor backward velocity. Although the tug-of-war involves >100 motors, values are calculated for a single molecule and reflect the collective dynein and non-collective kinesin functions when they work as a team. This assay would be useful for detailed in vitro analysis of intracellular motility, e.g., mitosis, where a large number of motors with mixed polarities are involved.
—  Ikuta J, et al. 2014

(TitleTug-of-war of microtubule filaments at the boundary of a kinesin- and dynein-patterned surface)