title: The structural kinetics of switch-1 and the neck linker explain the functions of kinesin-1 and Eg5.
abstract: Kinesins perform mechanical work to power a variety of cellular functions, from mitosis to organelle transport. Distinct functions shape distinct enzymologies, and this is illustrated by comparing kinesin-1, a highly processive transport motor that can work alone, to Eg5, a minimally processive mitotic motor that works in large ensembles. Although crystallographic models for both motors reveal similar structures for the domains involved in mechanochemical transduction--including switch-1 and the neck linker--how movement of these two domains is coordinated through the ATPase cycle remains unknown. We have addressed this issue by using a novel combination of transient kinetics and time-resolved fluorescence, which we refer to as "structural kinetics," to map the timing of structural changes in the switch-1 loop and neck linker. We find that differences between the structural kinetics of Eg5 and kinesin-1 yield insights into how these two motors adapt their enzymologies for their distinct functions.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Muretta
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697;
authors.forename: Yonggun
authors.initials: Y
authors.lastname: Jun
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697; Department of Physics, University of California, Irvine, CA 92697;
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.affiliation: Department of Cancer Biology, Lerner Research Institute of the Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Major
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455;
authors.forename: David D
authors.initials: DD
authors.lastname: Thomas
authors.affiliation: Department of Cancer Biology, Lerner Research Institute of the Cleveland Clinic Foundation, Cleveland, OH 44195 rosenfs@ccf.org.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012756:Sheep; D013696:Temperature
chemical_list: C470243:KIF11 protein, human; C488101:KIF5B protein, human; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D016547:Kinesins
keywords: fluorescence resonance energy transfer; kinesin; molecular motor; time-resolved fluorescence; transient kinetics