Cells depend on components being moved to the correct place at the correct time. My group is interested in cytoplasmic dynein-1 (dynein), a motor which delivers many different cargos via the microtubule network. When dynein is mutated it leads to neurodegeneration and it is susceptible to hijack by viruses which use it to travel into the cell. In the presence of cargo adaptor proteins, such as BICD, dynein binds a cofactor called dynactin. This generates a transporter complex capable of long distance movement along microtubules. We have used cryo-electron microscopy (cryo-EM) to determine a 4.0Å structure of dynactin that explains how this 23 subunit complex is assembled. We subsequently used cryo-EM, in vitro motility assays and in cell assays to determine why dynein is inhibited when it is on its own and how it is activated by binding dynactin. We are now working to understand how the cargo adaptors specifically recruit dynein to dynactin.
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