A structural change in the kinesin motor protein that drives motility.
Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.
Rice
S
S
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
Lin
A W
AW
Safer
D
D
Hart
C L
CL
Naber
N
N
Carragher
B O
BO
Cain
S M
SM
Pechatnikova
E
E
Wilson-Kubalek
E M
EM
Whittaker
M
M
Pate
E
E
Cooke
R
R
Taylor
E W
EW
Milligan
R A
RA
Vale
R D
RD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D003001:Cloning, Molecular; D020285:Cryoelectron Microscopy; D003545:Cysteine / Q000737:chemistry / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000502:physiology*; D016296:Mutagenesis; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods
D020409:Molecular Motor Proteins; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases; D016547:Kinesins; D003545:Cysteine