The structure of apo-kinesin bound to tubulin links the nucleotide cycle to movement.
Kinesin-1 is a dimeric ATP-dependent motor protein that moves towards microtubules (+) ends. This movement is driven by two conformations (docked and undocked) of the two motor domains carboxy-terminal peptides (named neck linkers), in correlation with the nucleotide bound to each motor domain. Despite extensive data on kinesin-1, the structural connection between its nucleotide cycle and movement has remained elusive, mostly because the structure of the critical tubulin-bound apo-kinesin state was unknown. Here we report the 2.2 Å structure of this complex. From its comparison with detached kinesin-ADP and tubulin-bound kinesin-ATP, we identify three kinesin motor subdomains that move rigidly along the nucleotide cycle. Our data reveal how these subdomains reorient on binding to tubulin and when ATP binds, leading respectively to ADP release and to neck linker docking. These results establish a framework for understanding the transformation of chemical energy into mechanical work by (+) end-directed kinesins.
Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre de Recherche de Gif, Centre National de la Recherche Scientifique, 1 avenue de la Terrasse, 91190 Gif sur Yvette, France.
Luyan
L
Cao
1] Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre de Recherche de Gif, Centre National de la Recherche Scientifique, 1 avenue de la Terrasse, 91190 Gif sur Yvette, France [2] Institute of Protein Research, Tongji University, 1239 SiPing Road, 200092 Shanghai, China.
Weiyi
W
Wang
Institute of Protein Research, Tongji University, 1239 SiPing Road, 200092 Shanghai, China.
Qiyang
Q
Jiang
Institute of Protein Research, Tongji University, 1239 SiPing Road, 200092 Shanghai, China.
Chunguang
C
Wang
Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre de Recherche de Gif, Centre National de la Recherche Scientifique, 1 avenue de la Terrasse, 91190 Gif sur Yvette, France.
Marcel
M
Knossow
Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre de Recherche de Gif, Centre National de la Recherche Scientifique, 1 avenue de la Terrasse, 91190 Gif sur Yvette, France.
Benoît
B
Gigant
D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000378:metabolism* / Q000502:physiology; D008870:Microtubules / Q000378:metabolism / Q000502:physiology; D062105:Molecular Docking Simulation; D009068:Movement / Q000502:physiology; D009711:Nucleotides / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014404:Tubulin / Q000378:metabolism* / Q000502:physiology
C488101:KIF5B protein, human; D009711:Nucleotides; D014404:Tubulin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D016547:Kinesins