Article
- The EMBO Journal (2006) 25, 4187 - 4194
- doi:10.1038/sj.emboj.7601299
Published online: 31 August 2006
Subject Categories:
High-resolution cryo-EM maps show the nucleotide binding pocket of KIF1A in open and closed conformations
Masahide Kikkawa1 and Nobutaka Hirokawa2
- Department of Cell Biology, Southwestern Medical Center, University of Texas, Dallas, TX, USA
- Department of Cell Biology and Anatomy, Graduate School of Medicine Hongo, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Correspondence to:
Nobutaka Hirokawa, Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. Tel.: +81 3 5841 3326; Fax: +81 3 5802 8646; E-mail: hirokawa@m.u-tokyo.ac.jp
Received 20 April 2006; Accepted 1 August 2006
Abstract
Kinesin is an ATP-driven microtubule (MT)-based motor fundamental to organelle transport. Although a number of kinesin crystal structures have been solved, the structural evidence for coupling between the bound nucleotide and the conformation of kinesin is elusive. In addition, the structural basis of the MT-induced ATPase activity of kinesin is not clear because of the absence of the MT in the structure. Here, we report cryo-electron microscopy structures of the monomeric kinesin KIF1A–MT complex in two nucleotide states at about 10 Å resolution, sufficient to reveal the secondary structure. These high-resolution maps visualized clear structural changes that suggest a mechanical pathway from the nucleotide to the neck linker via the motor core rotation. In addition, new nucleotide binding pocket conformations are observed that are different from X-ray crystallographic structures; it is closed in the 5'-adenylyl-imidodiphosphate state, but open in the ADP state. These results suggest a structural model of biased diffusion movement of monomeric kinesin motor.
Keywords:
- cryo-electron microscopy,
- kinesin,
- microtubule
