Cse1 mediates nuclear export of importin α, the nuclear localization signal (NLS) import adaptor. We report the 3.1 Å resolution structure of cargo-free Cse1, representing this HEAT repeat protein in its cytosolic state. Cse1 is compact, consisting of N- and C-terminal arches that interact to form a ring. Comparison with the structure of cargo-bound Cse1 shows a major conformational change leading to opening of the structure upon cargo binding. The largest structural changes occur within a hinge region centered at HEAT repeat 8. This repeat contains a conserved insertion that connects the RanGTP and importin α contact sites and that is essential for binding. In the cargo-free state, the RanGTP binding sites are occluded and the importin α sites are distorted. Mutations that destabilize the N- to C-terminal interaction uncouple importin α and Ran binding, suggesting that the closed conformation prevents association with importin α.