The structure and mechanism of the dynein/dynactin transport machine.
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Movement is one of the defining characteristics of life and at the sub-cellular level many motions are driven by motor proteins walking along the actin and microtubule tracks that extend throughout the cytoplasm. My group is specifically interested in cytoplasmic dynein: a multi-protein complex that is arguably one of the most interesting and least studied of all these motors.
Work on dynein has until recently been hindered by its large size and complexity. Now, however, the tools are becoming available that are allowing us to tackle its structure and address questions such as how it generates movement and how it interacts specifically with the many different cargos in carries. Dynein works together with a >23 subunit cofactor called dynactin that is built around a filament of an actin-like protein called Arp1. How dynactin is assembled and how all its components contribute to dynein function is not yet known.
This PhD project will use structural approaches (cryo-electron microscopy and cryo-electron tomography), together with protein biochemistry and single molecule fluorescence microscopy to investigate the role dynactin plays in dynein transport. It will also address the question of how the dynactin complex is assembled.
Belyy, V., Schlager, M.A., Foster, H., Reimer, A.E., Carter, A.P. and Yildiz, A. (2016)
The mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition.
Nat Cell Biol. doi: 10.1038/ncb3393.
Urnavicius, L., Zhang, K., Diamant, A.G., Motz, C., Schlager, M.A., Yu, M., Patel, N.A., Robinson, C.V. and Carter, A.P. (2015)
The structure of the dynactin complex and its interaction with dynein.
Schmidt, H., Zalyte, R., Urnavicius, L. and Carter, A.P. (2015)
Structure of human cytoplasmic dynein-2 primed for its power stroke.
Schlager, M.A., Hoang, H.T., Urnavicius, L., Bullock, S.L. and Carter, A.P. (2014)
In vitro reconstitution of a highly processive recombinant human dynein complex.
EMBO J. 33(17):1855-68.