Transporting cargos over long distances: insight from dynein/dynactin structures
Date:
Wednesday, March 1, 2017 13:00 - 14:00
Speaker:
Andrew Carter (MRC Laboratory of Molecular Biology)
Location:
Mondi Seminar Room 2, Central Building
Series:
Life Sciences Seminar
Host:
Martin Loose
Contact:
SIX Rita
Cells depend on components being moved to the correct place at the correct time. My group is interested in cytoplasmic dynein-1 (dynein-1), a motor which delivers many different cargos via the microtubule network. When dynein-1 is mutated it leads to neurodegeneration and it is susceptible to hijack by viruses which use it to travel into the cell. We have determined X-ray crystal structures of the dynein motor before and after it binds and hydrolyses ATP. We subsequently used single molecule fluorescence assays to show how a cofactor, dynactin, activates the full length 1.4MDa dynein complex to move long distances along microtubules. A high resolution (4.0Å) cryo-electron microscopy (cryo-EM) structure of dynactin explained how this 23 subunit complex is assembled. We also used a combination of cryo-EM and X-ray crystallography to show how dynactin binds to dynein. The two complexes are only brought together in the presence of an adaptor protein, Bicaudal-D2, that links them to the cargo they will carry. This suggests the large and intricate dynein/dynactin transport machine only assembles when a cargo is ready to move.