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Image of the Week: Structure of the dynactin complex

27 Mar, 2015
Structure of the dynactin complex

Image courtesy of Urnavicus et al, made by Janet Iwasa (University of Utah)

This image shows a model of a tiny protein machine that moves things around within our cells. A new study reveals how the motor called dynein (grey) is attached to its cargo via an adaptor protein (orange). The attachment requires the help of another protein complex called dynactin (multi-coloured).

The dynein/dynactin machine drags its cargo along tracks called microtubules that stretch throughout the cell (a short section of microtubule is shown in green in the bottom left of the image). It takes things from where they are made to where they are needed.

When things go wrong with the dynein machinery it can result in neurodegenerative diseases such as motor neuron diseases, dementias or a form of Parkinson’s disease.  This intracellular transport mechanism can also be commandeered by viruses, such as those that cause herpes, cold sores, chicken pox and shingles.

A Wellcome Trust funded team of researchers, led by Dr Andrew Carter at the MRC Lab of Molecular Biology in Cambridge, have used a state of the art cryo-electron microscope to determine the structure of dynactin and show how it helps dynein bind to the cargo adaptor Bicaudal-D2.  Examples of the high-resolution cryo-electron microscopy maps are shown in the background of the image.

A great mystery in the field of cellular transport is why dynein requires dynactin. Carter and his team have revealed for the first time that they both form an intricate complex with the cargo adaptor sandwiched between them. This suggests dynactin acts as an “on switch” that activates dynein to move for long distances along microtubules.

The team expects that each different cargo, for example mitochondria, mRNAs, toxic aggregated proteins and different small transport vesicles, will have different adaptors. Future work will focus on whether they all bind in the same way as Bicaudal-D2, how dynein defects cause neurodegenerative diseases and whether it is possible to block it from carrying viruses.

The team’s research is the cover story on this week’s Science, and you can read the full paper online. To find out more about Dr Carter’s work, visit his website.

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