Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of a ∼15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule ‘plus’ end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when γ-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.
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We thank L. Sweeney for encouragement; A. Ruby for assistance with protein preparations; B. Sheehan for computing and image processing; and M. Tomishige for examining the processivity of cys-light K560–GFP. We thank R. Case and K. Thorn for comments on the manuscript. This work was supported, in part, by grants for the NIH (R.A.M., E.W.T., R.C. and R.D.V.), and the NSF (B.O.C.). S.R. is supported by the UCSF Graduate Group in Biophysics.
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Rice, S., Lin, A., Safer, D. et al. A structural change in the kinesin motor protein that drives motility. Nature 402, 778–784 (1999) doi:10.1038/45483
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