Thomas G.Wendt, Niels Volkmann1,

We used cryo-electron microscopy and image recon-struction to investigate the structure and microtubule-binding con®gurations of dimeric non-claret disjunc-tional (ncd) motor domains under various nucleotide conditions, and applied molecular docking using ncd's dimeric X-ray structure to generate a mechan-istic model for force transduction. To visualize the a-helical coiled-coil neck better, we engineered an SH3 domain to the N-terminal end of our ncd construct (296±700). Ncd exhibits strikingly different nucleo-tide-dependent three-dimensional conformations and microtubule-binding patterns from those of conven-tional kinesin. In the absence of nucleotide, the neck adapts a con®guration close to that found in the X-ray structure with stable interactions between the neck and motor core domain. Minus-end-directed move-ment is based mainly on two key events: (i) the stable neck±core interactions in ncd generate a binding geometry between motor and microtubule which places the motor ahead of its cargo in the minus-end direction; and (ii) after the uptake of ATP, the two heads rearrange their position relative to each other in a way that promotes a swing of the neck in the minus-end direction