An ATP gate controls tubulin binding by the tethered head of kinesin-1.
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.
Alonso
Maria C
MC
Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.
Drummond
Douglas R
DR
Kain
Susan
S
Hoeng
Julia
J
Amos
Linda
L
Cross
Robert A
RA
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*
D020409:Molecular Motor Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D016547:Kinesins