title: KIF1D is a fast non-processive kinesin that demonstrates novel K-loop-dependent mechanochemistry.
abstract: The KIF1 subfamily members are monomeric and contain a number of amino acid inserts in surface loops. A particularly striking insertion of several lysine/arginine residues occurs in L12 and is called the K-loop. Two recent studies have employed both kinetic and single-molecule methods to investigate KIF1 motor properties and have produced very different conclusions about how these motors generate motility. Here we show that a hitherto unstudied member of this group, KIF1D, is not chemically processive and drives fast motility despite demonstrating a slow ATPase. The K-loop of KIF1D was analysed by deletion and insertion mutagenesis coupled with characterization by steady state and transient kinetics. Together, the results indicate that the K-loop not only increases the affinity of the motor for the MT, but crucially also inhibits its subsequent isomerization from weak to strong binding, with coupled ADP release. By stabilizing the weak binding, the K-loop establishes a pool of motors primed to undergo their power stroke.
authors.affiliation: Molecular Motors Group, Marie Curie Research Institute, Oxted, Surrey RH8 0TL, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Rogers
authors.forename: S
authors.initials: S
authors.lastname: Weiss
authors.forename: I
authors.initials: I
authors.lastname: Crevel
authors.forename: P J
authors.initials: PJ
authors.lastname: Brophy
authors.forename: M
authors.initials: M
authors.lastname: Geeves
authors.forename: R
authors.initials: R
authors.lastname: Cross
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009068:Movement; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D062367:ortho-Aminobenzoates / Q000378:metabolism
chemical_list: C110237:KIF1D protein, mouse; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D062367:ortho-Aminobenzoates; D000244:Adenosine Diphosphate; C081523:3'-O-(N-methylanthraniloyl)adenosine 5'-diphosphate; D016547:Kinesins