Congruent docking of dimeric kinesin and ncd into three-dimensional electron cryomicroscopy maps of microtubule-motor ADP complexes

We present a new map showing dimeric kinesin bound to microtubules in the p resence of ADP that was obtained by electron cryomicroscopy and image recon struction. The directly bound monomer (first head) shows a different confor mation from one in the more tightly bound empty state. This change in the f irst head is amplified as a movement of the second (tethered) head, which t ilts upward. The atomic coordinates of kinesin ADP dock into our map so tha t the tethered head associates with the bound head as in the kinesin dimer structure seen by x-ray crystallography. The new docking orientation avoids problems associated with previous predictions; it puts residues implicated by proteolysis-protection and mutagenesis studies near the microtubule but does not lead to steric interference between the coiled-coil tail and the microtubule surface. The observed conformational changes in the tightly bou nd states would probably bring some important residues closer to tubulin. A s expected from the homology with kinesin, the atomic coordinates of noncla ret disjunctional protein (ncd).ADP dock in the same orientation into the a ttached head in a map of microtubules decorated with dimeric ncd ADP. Our r esults support the idea that the observed direct interaction between the tw o heads is important at some stages of the mechanism by which kinesin moves processively along microtubules.