Large Conformational Changes in a Kinesin Motor Catalyzed by Interaction with Microtubules

• Published in: Molecular cell Vol. 23; no. 6; pp. 913 - 923
• Main Authors: Hirose, Keiko, Akimaru, Erika, Akiba, Toshihiko, Endow, Sharyn A., Amos, Linda A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2006
• Subjects: Adenosine Diphosphate - chemistry; Adenosine Diphosphate - metabolism; Adenylyl Imidodiphosphate - chemistry; Adenylyl Imidodiphosphate - metabolism; Binding Sites; CELLBIO; Cryoelectron Microscopy; Crystallography, X-Ray; Kinesins - chemistry; Kinesins - metabolism; Kinesins - ultrastructure; Microtubules - chemistry; Microtubules - metabolism; Microtubules - ultrastructure; Models, Molecular; Protein Structure, Tertiary; Tubulin - chemistry; Tubulin - metabolism; Tubulin - ultrastructure; CELLBIO
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2006.07.020

Kinesin motor proteins release nucleotide upon interaction with microtubules (MTs), then bind and hydrolyze ATP to move along the MT. Although crystal structures of kinesin motors bound to nucleotides have been solved, nucleotide-free structures have not. Here, using cryomicroscopy and three-dimensional (3D) reconstruction, we report the structure of MTs decorated with a Kinesin-14 motor, Kar3, in the nucleotide-free state, as well as with ADP and AMPPNP, with resolution sufficient to show α helices. We find large structural changes in the empty motor, including melting of the switch II helix α4, closure of the nucleotide binding pocket, and changes in the central β sheet reminiscent of those reported for nucleotide-free myosin crystal structures. We propose that the switch II region of the motor controls docking of the Kar3 neck by conformational changes in the central β sheet, similar to myosin, rather than by rotation of the motor domain, as proposed for the Kif1A kinesin motor.