Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, 
are motors that move towards the minus ends of microtubules. Cytoplasmic 
dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport, and is 
implicated in viral infections and neurodegenerative diseases. Cytoplasmic 
dynein-2 (dynein-2) performs intraflagellar transport and is associated with 
human skeletal ciliopathies. Dyneins share a conserved motor domain that couples 
cycles of ATP hydrolysis with conformational changes to produce movement. Here 
we present the crystal structure of the human cytoplasmic dynein-2 motor bound 
to the ATP-hydrolysis transition state analogue ADP.vanadate. The structure 
reveals a closure of the motor's ring of six AAA+ domains (ATPases associated 
with various cellular activites: AAA1-AAA6). This induces a steric clash with 
the linker, the key element for the generation of movement, driving it into a 
conformation that is primed to produce force. Ring closure also changes the 
interface between the stalk and buttress coiled-coil extensions of the motor 
domain. This drives helix sliding in the stalk which causes the microtubule 
binding domain at its tip to release from the microtubule. Our structure answers 
the key questions of how ATP hydrolysis leads to linker remodelling and 
microtubule affinity regulation.