Structural biology of molecular machines

Nature has evolved fascinating molecular machines that are responsible for essential biological processes like DNA synthesis, protein translation or the generation of movement along cytoskeletal tracks. The latter task is carried out by motor proteins. Cells rely on these motor proteins because the cytosol is a crowded and highly viscos environment making active transport processes necessary to ensure proper distribution of vital factors. Among the large family of motor proteins, the dynein motor stands out because of its huge size of around 1.2 MDa and the complexity of its subunit composition. This ATP dependent molecular machine transports various essential cargos, including whole organelles like endosomes, mitochondria or nuclei, along microtubules. Especially nuclear transport processes involving dynein have attracted a lot of attention, because of their importance for developmental processes. Some of the most prominent examples include the fusion of male and female pro-nuclei after fertilization, the interkinetic nuclear migration during embryonic brain development or the nuclear movements during C.elegans hypodermal syncytium formation.  We use an integrated structural biology approach that combines cryo-electron microscopy and x-ray crystallography to elucidate how the dynein motor produces force to generate movement and how it connects to and transports nuclei.