title: An ATP gate controls tubulin binding by the tethered head of kinesin-1.
abstract: Kinesin-1 is a two-headed molecular motor that walks along microtubules, with each step gated by adenosine triphosphate (ATP) binding. Existing models for the gating mechanism propose a role for the microtubule lattice. We show that unpolymerized tubulin binds to kinesin-1, causing tubulin-activated release of adenosine diphosphate (ADP). With no added nucleotide, each kinesin-1 dimer binds one tubulin heterodimer. In adenylyl-imidodiphosphate (AMP-PNP), a nonhydrolyzable ATP analog, each kinesin-1 dimer binds two tubulin heterodimers. The data reveal an ATP gate that operates independently of the microtubule lattice, by ATP-dependent release of a steric or allosteric block on the tubulin binding site of the tethered kinesin-ADP head.
authors.affiliation: Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Alonso
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Drummond
authors.forename: Susan
authors.initials: S
authors.lastname: Kain
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.forename: Linda
authors.initials: L
authors.lastname: Amos
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cross
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism*; D009491:Neurospora; D011487:Protein Conformation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020409:Molecular Motor Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D016547:Kinesins