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Science 30 July 2004:
Vol. 305. no. 5684, pp. 678 - 683
DOI: 10.1126/science.1096621
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Reports

KIF1A Alternately Uses Two Loops to Bind Microtubules

Ryo Nitta,1 Masahide Kikkawa,1,2 Yasushi Okada,1 Nobutaka Hirokawa1*

The motor protein kinesin moves along microtubules, driven by adenosine triphosphate (ATP) hydrolysis. However, it remains unclear how kinesin converts the chemical energy into mechanical movement. We report crystal structures ofmonomeric kinesin KIF1A with three transition-state analogs: adenylyl imidodiphosphate (AMP-PNP), adenosine diphosphate (ADP)–vanadate, and ADP-AlFx (aluminofluoride complexes). These structures, together with known structures of the ADP-bound state and the adenylyl-(ß,{gamma}-methylene) diphosphate (AMP-PCP)–bound state, show that kinesin uses two microtubule-binding loops in an alternating manner to change its interaction with microtubules during the ATP hydrolysis cycle; loop L11 is extended in the AMP-PNP structure, whereas loop L12 is extended in the ADP structure. ADP-vanadate displays an intermediate structure in which a conformational change in two switch regions causes both loops to be raised from the microtubule, thus actively detaching kinesin.

1 Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
2 Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.

* To whom correspondence should be addressed. E-mail: hirokawa{at}m.u-tokyo.ac.jp

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