KIF1A alternately uses two loops to bind microtubules.
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 of monomeric 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-(beta,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.
Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ryo
R
Nitta
Masahide
M
Kikkawa
Yasushi
Y
Okada
Nobutaka
N
Hirokawa
D000255:Adenosine Triphosphate / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D000535:Aluminum / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005459:Fluorides / Q000378:metabolism; D006860:Hydrogen Bonding; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014638:Vanadates / Q000378:metabolism
C490576:Kif1a protein, mouse; D009419:Nerve Tissue Proteins; D010710:Phosphates; D000266:Adenylyl Imidodiphosphate; D014638:Vanadates; D000255:Adenosine Triphosphate; D000535:Aluminum; D016547:Kinesins; D005459:Fluorides