title: A metal switch for controlling the activity of molecular motor proteins.
abstract: Kinesins are molecular motors that require a divalent metal ion (for example, Mg(2+)) to convert the energy of ATP hydrolysis into directed force production along microtubules. Here we present the crystal structure of a recombinant kinesin motor domain bound to Mn(2+) and ADP and report on a serine-to-cysteine substitution in the switch 1 motif of kinesin that allows its ATP hydrolysis activity to be controlled by adjusting the ratio of Mn(2+) to Mg(2+). This mutant kinesin binds ATP similarly in the presence of either metal ion, but its ATP hydrolysis activity is greatly diminished in the presence of Mg(2+). In human kinesin-1 and kinesin-5 as well as Drosophila melanogaster kinesin-10 and kinesin-14, this defect is rescued by Mn(2+), providing a way to control both the enzymatic activity and force-generating ability of these nanomachines.
authors.affiliation: Dartmouth College, Department of Chemistry, Hanover, New Hampshire, USA.
authors.forename: Jared C
authors.initials: JC
authors.lastname: Cochran
authors.forename: Yu Cheng
authors.initials: YC
authors.lastname: Zhao
authors.forename: Dean E
authors.initials: DE
authors.lastname: Wilcox
authors.forename: F Jon
authors.initials: FJ
authors.lastname: Kull
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006868:Hydrolysis; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D008345:Manganese / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D029721:Drosophila Proteins; C488101:KIF5B protein, human; D020409:Molecular Motor Proteins; C066696:ncd protein, Drosophila; D008345:Manganese; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C080298:Nod protein, Drosophila; D016547:Kinesins; D008274:Magnesium