title: Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin.
abstract: Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg(2+) release. On the basis of new structural and mutagenesis data, we propose a model mechanism for microtubule activation of Mg-ADP release from KIF1A. In our model, a specific interaction between loop L7 of KIF1A and beta-tubulin reconfigures the KIF1A active site by shifting the relative positions of switches I and II. This leads to the sequential release of a group of water molecules that sits over the Mg(2+) in the active site, followed by Mg(2+) and finally the ADP. We further propose that this set of events is linked to a strain-dependent docking of the neck linker to the motor core, which produces a two-step power stroke.
authors.affiliation: Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nitta
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okada
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hirokawa
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C490576:Kif1a protein, mouse; D000244:Adenosine Diphosphate; D016547:Kinesins; D008274:Magnesium