Kinesin’s tail domain is an inhibitory regulator of the motor domain


When not bound to cargo, the motor protein kinesin is in an inhibited state that has low microtubule-stimulated ATPase activity. Inhibition serves to minimize the dissipation of ATP and to prevent mislocalization of kinesin in the cell. Here we show that this inhibition is relieved when kinesin binds to an artificial cargo. Inhibition is mediated by kinesin’s tail domain: deletion of the tail activates the ATPase without need of cargo binding, and inhibition is re-established by addition of exogenous tail peptide. Both ATPase and motility assays indicate that the tail does not prevent kinesin from binding to microtubules, but rather reduces the motor’s stepping rate.

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Figure 1: Structural model for kinesin and its regulation.
Figure 2: Coomassie-stained SDS–polyacrylamide gels of wild-type and mutant kinesin proteins.
Figure 3: Kinesin’s ATPase rate is activated by cargo binding or by deletion of its tail domain.
Figure 4: Exogenous kinesin tail protein inhibits kinesin’s ATPase activity and motility.
Figure 5: A structural model of tail-mediated inhibition.


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We thank A. Hunter, P. Detwiler, E. Lumpkin and R. Sawhney for comments on an earlier version of this manuscript. This work was supported by NIH grant AR40593 (to J.H.). D.L.C. was supported by NIH Molecular Biophysics Training Grant GM08268 and by the Achievement Reward for College Scientists.

Correspondence and requests for materials should be addressed to J.H. The vectors encoding the following proteins have been deposited at GenBank under the indicated accession numbers: vector pPK113 (kinesin α2), AF053733; pPK121 (kinesin α2β2), AF055298; pPK115 (Δhinge), AF117643; pH911 (tail-911), AF117644; pPK124 (Δtail), AF161077; p864INS (tail-864), AF116269.

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Correspondence to Jonathon Howard.

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Coy, D., Hancock, W., Wagenbach, M. et al. Kinesin’s tail domain is an inhibitory regulator of the motor domain. Nat Cell Biol 1, 288–292 (1999).

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