Structure of the complex of a mitotic kinesin with its calcium binding regulator

Department of Biochemistry/Biophysics, University of California, San Francisco, CA 94107, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2009; 106(20):8175-9. DOI: 10.1073/pnas.0811131106
Source: PubMed


Much of the transport, tension, and movement in mitosis depends on kinesins, the ATP-powered microtubule-based motors. We report the crystal structure of a kinesin complex, the mitotic kinesin KCBP bound to its principal regulator KIC. Shown to be a Ca(2+) sensor, KIC works as an allosteric trap. Extensive intermolecular interactions with KIC stabilize kinesin in its ADP-bound conformation. A critical component of the kinesin motile mechanism, called the neck mimic, switches its association from kinesin to KIC, stalling the motor. KIC denies access of the motor to its track by steric interference. Two major features of this regulation, allosteric trapping and steric blocking, are likely to be general for all kinesins.

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    • "However, a principle difficulty in structural analysis of the kinesin system, as with the other two known cytoskeletal motors (myosin and dynein), has been the inability to obtain atomic-resolution structures of the motor while complexed to the partner filament. To date, the only atomic-resolution structural data available for kinesin comes from X-ray crystal structures of the molecule by itself (Marx et al. 2009) or in complex with a regulatory partner (Vinogradova et al. 2009). However, kinesin’s enzymatic properties change markedly in the absence of microtubules, where for example the ATPase rate drops to a basal level ∼1,000-fold reduced over the motile, microtubule-attached state (Hackney 1988). "
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