title: A structural change in the kinesin motor protein that drives motility.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rice
authors.forename: A W
authors.initials: AW
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Safer
authors.forename: C L
authors.initials: CL
authors.lastname: Hart
authors.forename: N
authors.initials: N
authors.lastname: Naber
authors.forename: B O
authors.initials: BO
authors.lastname: Carragher
authors.forename: S M
authors.initials: SM
authors.lastname: Cain
authors.forename: E
authors.initials: E
authors.lastname: Pechatnikova
authors.forename: E M
authors.initials: EM
authors.lastname: Wilson-Kubalek
authors.forename: M
authors.initials: M
authors.lastname: Whittaker
authors.forename: E
authors.initials: E
authors.lastname: Pate
authors.forename: R
authors.initials: R
authors.lastname: Cooke
authors.forename: E W
authors.initials: EW
authors.lastname: Taylor
authors.forename: R A
authors.initials: RA
authors.lastname: Milligan
authors.forename: R D
authors.initials: RD
authors.lastname: Vale
mesh_terms: 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
chemical_list: D020409:Molecular Motor Proteins; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases; D016547:Kinesins; D003545:Cysteine