• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar
MRC Laboratory of Molecular Biology

MRC Laboratory of Molecular Biology

One of the world's leading research institutes, our scientists are working to advance understanding of biological processes at the molecular level - providing the knowledge needed to solve key problems in human health.

  • Home
  • About LMB
  • Research
  • Research Groups
  • Students
  • Recruitment
  • Life at the LMB
  • Achievements
  • News & Events
Home > Insight on Research > Cryo-EM reveals first high-resolution structure of the dynein-dynactin complex bound to microtubules

Cryo-EM reveals first high-resolution structure of the dynein-dynactin complex bound to microtubules

Published on 7 September, 2022

New structure reveals how dynein motor domains interact and how a pair of cargo adaptors use conserved sequence motifs to scaffold the motor protein complex

Cryo-EM structure of the dynein motile machinery showing the dynein motor domains binding to microtubules and a pair of coiled-coil cargo adaptors scaffolding the complex

To transport cargos along cytoskeletal filaments, cells rely on motor proteins. Dynein, a large motor protein complex, travels on microtubules and is responsible for transporting numerous cargos. To activate for transport, dynein binds its cofactor dynactin and an adaptor which attaches the complex to cargos. Understanding precisely how these cargo adaptors recruit dynein-dynactin, and how the resulting complex moves has so far been limited by a lack of high-resolution structural information. Now Sami Chaaban and Andrew Carter, in the LMB’s Structural Studies Division, have used electron cryo-microscopy (cryo-EM) to solve the structure of the complex bound to microtubules.

The resulting structure shows how dynein’s motor domains interact with each other and how a pair of cargo adaptors use conserved sequence motifs to scaffold the complex. These results help illustrate dynein’s stepping behaviour and how it attaches to its cargos.

To achieve this, the pair had to develop a technique to overcome the challenges of using cryo-EM to visualise proteins that sparsely decorate filaments. Sami, a member of Andrew’s group, locked the dynein-dynactin complexes in a state which tightly binds microtubules and isolates them from unbound complexes for cryo-EM visualization. In order to overcome the microtubules’ dominant signal, Sami solved the structures of the microtubules and computationally subtracted them from the micrographs. Single particle analysis techniques allowed the pair to then solve the structure of the dynein-dynactin complexes. This method has the potential to be applied to other difficult complexes decorating filaments.

This structure offers greater insights into the behaviour of dynein, an important breakthrough given its myriad roles in cells and frequent hijacking by viruses that enter our cells. Furthermore, mutations affecting dynein and its cofactors have been implicated in various diseases, including development neuropathies. Enhanced understanding of the dynein machinery is therefore an important step towards understanding how these diseases develop.

This work was funded by UKRI MRC, Wellcome and EMBO.

Further references

Structure of dynein-dynactin on microtubules shows tandem adaptor binding. Chaaban, S., Carter, AP. Nature
Andrew’s group page

Previous Insight on Research articles

Packaging molecular motors for delivery
Engineering dynein to move backwards to understand how it moves forwards

Primary Sidebar

Search

  • Privacy & Cookies
  • Contact Directory
  • Freedom of Information
  • Site Map
Find Us
©2025 MRC Laboratory of Molecular Biology,
Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. 01223 267000

The MRC is part of UK Research and Innovation

Contact Us

This site uses cookies. The LMB may use cookies to analyse how you use our website. We use external analysis systems which may set additional cookies to perform their analysis. These cookies (and any others in use) are detailed in our Privacy and Cookies Policy and are integral to our website. You can delete or disable these cookies in your web browser if you wish, but then our site may not work as it is designed. Ok