The crystal structure of the minus-end-directed microtubule motor protein ncd reveals variable dimer conformations

Background: The kinesin superfamily of microtubule-associated motor protein s are important for intracellular transport and for cell division in eukary otes. Conventional kinesins have the motor domain at the N terminus of the heavy chain and move towards the plus end of microtubules. The ncd protein is necessary for chromosome segregation in meiosis. It belongs to a subfami ly of kinesins that have the motor domain at the C terminus and move toward s the minus end of microtubules. Results: The crystal structure of dimeric nod has been obtained at 2.9 Angs trom resolution from crystals with the C222, space group, with two independ ent dimers per asymmetric unit. The motor domains in these dimers are not r elated by crystallographic symmetry and the two nod dimers have significant ly different conformations. An alpha-helical coiled coil connects, and inte racts with, the motor domains. Conclusions: The ncd protein has a very compact structure, largely due to e xtended interactions of the coiled coil with the head domains. Despite this , we find that the overall conformation of the ncd dimer can be rotated by as much as 10 degrees away from that of the twofold-symmetric archetypal nc d. The crystal structures of conventional kinesin and of ncd suggest a stru ctural rationale for the reversal of the direction of movement in chimeric kinesins.