Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 July 2004:
Vol. 305. no. 5684, pp. 678 - 683
DOI: 10.1126/science.1096621
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A kinesin-13 mutant catalytically depolymerizes microtubules in ADP.
M. Wagenbach, S. Domnitz, L. Wordeman, and J. Cooper (2008)
J. Cell Biol. 183, 617-623
   Abstract »    Full Text »    PDF »
Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics.
N. Hirokawa and Y. Noda (2008)
Physiol Rev 88, 1089-1118
   Abstract »    Full Text »    PDF »
A cool look at the structural changes in kinesin motor domains.
L. A. Amos and K. Hirose (2007)
J. Cell Sci. 120, 3919-3927
   Abstract »    Full Text »    PDF »
The beginning of kinesin's force-generating cycle visualized at 9-A resolution.
C. V. Sindelar and K. H. Downing (2007)
J. Cell Biol. 177, 377-385
   Abstract »    Full Text »    PDF »
Structure of Human Eg5 in Complex with a New Monastrol-based Inhibitor Bound in the R Configuration.
I. Garcia-Saez, S. DeBonis, R. Lopez, F. Trucco, B. Rousseau, P. Thuery, and F. Kozielski (2007)
J. Biol. Chem. 282, 9740-9747
   Abstract »    Full Text »    PDF »
Internal strain regulates the nucleotide binding site of the kinesin leading head.
C. Hyeon and J. N. Onuchic (2007)
PNAS 104, 2175-2180
   Abstract »    Full Text »    PDF »
Kinetic and Mechanistic Basis of the Nonprocessive Kinesin-3 Motor NcKin3.
S. Adio, M. Bloemink, M. Hartel, S. Leier, M. A. Geeves, and G. Woehlke (2006)
J. Biol. Chem. 281, 37782-37793
   Abstract »    Full Text »    PDF »
Backsteps induced by nucleotide analogs suggest the front head of kinesin is gated by strain.
N. R. Guydosh and S. M. Block (2006)
PNAS 103, 8054-8059
   Abstract »    Full Text »    PDF »
Kinetic Mechanism of Myosin IXB and the Contributions of Two Class IX-specific Regions.
V. Nalavadi, M. Nyitrai, C. Bertolini, N. Adamek, M. A. Geeves, and M. Bahler (2005)
J. Biol. Chem. 280, 38957-38968
   Abstract »    Full Text »    PDF »
Initiation of the power stroke in muscle: Insights from the phosphate analog AlF4.
T. Kraft, E. Mahlmann, T. Mattei, and B. Brenner (2005)
PNAS 102, 13861-13866
   Abstract »    Full Text »    PDF »
Mutant Kinesin-2 Motor Subunits Increase Chromosome Loss.
M. S. Miller, J. M. Esparza, A. M. Lippa, F. G. Lux III, D. G. Cole, and S. K. Dutcher (2005)
Mol. Biol. Cell 16, 3810-3820
   Abstract »    Full Text »    PDF »
Removal of Tightly Bound ADP Induces Distinct Structural Changes of the Two Tryptophan-Containing Regions of the ncd Motor Domain.
H. Morii, T. Shimizu, N. Mizuno, M. Edamatsu, K. Ogawa, Y. Shimizu, and Y. Y. Toyoshima (2005)
J. Biochem. 138, 95-104
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)