Schmidt H, Gleave ES, Carter AP. (2012)
Insights into dynein motor domain function from a 3.3-Å crystal structure.
Nat Struct Mol Biol. Mar 14. doi: 10.1038/nsmb.2272.
Carter, A.P., Cho, C., Jin, L., Vale, R.D. (2011)
Crystal structure of the dynein motor domain.
Science 331:1159-65
Carter, A.P., Garbarino, J.E., Wilson-Kubalek, E.M., Shipley, W.E., Cho, C., Milligan, R.A., Vale, R.D., Gibbons, I.R. (2008)
Structure and functional role of dynein's microtubule-binding domain.
Science 322:1691-5
Reck-Peterson, S.L., Yildiz, A., Carter, A.P., Gennerich, A., Zhang, N., and Vale, R.D. (2006)
Single molecule analysis of dynein processivity and stepping behavior.
Cell 126:335-348.
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Group Members
- Helgo Schmidt
- Emma Gleave
- Max Schlager
- Aristides Diamant
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The contents of eukaryotic cells are organised and moved around by motor proteins running along the tracks that make up the cytoskeleton (microtubules and actin filaments). The largest and most complicated of these is the microtubule motor cytoplasmic dynein. It is involved with numerous processes, from carrying organelles and viruses, to cell division, to clearing up misfolded proteins. Our group is interested in the many structural and mechanistic questions that surround dynein. These include: what it looks like at an atomic level; how it selects which cargos to carry and how it generates movement.
In order to answer these and other questions, we will use a range of techniques with a
focus on x-ray crystallography. We will take advantage of recent developments which allow expression and manipulation of dynein in the bakers yeast Saccharomyces cerevisiae. In order to complement structural approaches we will also work on the mechanism of dynein using single molecule techniques, including recent methodology (FIONA) that allows the movement of different parts of the motor to be tracked to within a few nanometers.
 High precision tracking of a single molecule of cytoplasmic dynein as it steps along a microtubule. The xy position of dynein, labelled with a fluorescent quantum dot, is plotted on a grid whose spacing represents that of tubulin subunits in the microtubule. Movement (left to right) is characterised by rapid jumps followed by long pauses (clusters of spots coloured alternately in red and blue). The center of these pause sites (purple squares) corresponds to the spacing between binding sites on the microtubule.
A model of the cytoplasmic dynein motor domain: Force is generated by movement of the linker (purple) in response to binding and hydrolysis of ATP. The linker spans across a ring of ATP binding, AAA+ domains (colored blue to red). The long stalk (modeled here in white) protrudes out of the fourth AAA+ domain (yellow) and has the microtubule binding domain at its tip. Its base is supported by a protrusion from fifth AAA+ domain (orange) called the "buttress". Insets show details of the linker-ring interaction site (left) and nucleotide binding at the third AAA+ domain (right).
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Group Leaders 
