Switch-based mechanism of kinesin motors.
Kinesin motors are specialized enzymes that use hydrolysis of ATP to generate force and movement along their cellular tracks, the microtubules. Although numerous biochemical and biophysical studies have accumulated much data that link microtubule-assisted ATP hydrolysis to kinesin motion, the structural view of kinesin movement remains unclear. This study of the monomeric kinesin motor KIF1A combines X-ray crystallography and cryo-electron microscopy, and allows analysis of force-generating conformational changes at atomic resolution. The motor is revealed in its two functionally critical states-complexed with ADP and with a non-hydrolysable analogue of ATP. The conformational change observed between the ADP-bound and the ATP-like structures of the KIF1A catalytic core is modular, extends to all kinesins and is similar to the conformational change used by myosin motors and G proteins. Docking of the ADP-bound and ATP-like crystallographic models of KIF1A into the corresponding cryo-electron microscopy maps suggests a rationale for the plus-end directional bias associated with the kinesin catalytic core.
Kikkawa
M
M
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan.
Sablin
E P
EP
Okada
Y
Y
Yajima
H
H
Fletterick
R J
RJ
Hirokawa
N
N
D000244:Adenosine Diphosphate / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000502:physiology; D020134:Catalytic Domain; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D016547:Kinesins / Q000737:chemistry / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
C094065:KIF1A protein, human; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D016547:Kinesins