title: Modular aspects of kinesin force generation machinery.
abstract: The motor head of kinesin carries out microtubule binding, ATP hydrolysis, and force generation. Despite a high level of sequence and structural conservation, subtle variations in subdomains of the motor head determine family-specific properties. In particular, both Kinesin-1 (Kin-1) and Kinesin-5 (Kin-5) walk processively to the microtubule plus-end, yet show distinct motility characteristics suitable for their functions. We studied chimeric Kin-1/Kin-5 constructs with a combination of single molecule motility assays and molecular dynamics simulations to demonstrate that Kin-5 possesses a force-generating element similar to Kin-1, i.e., the cover-neck bundle. Furthermore, the Kin-5 neck linker makes additional contacts with the core of the motor head via loop L13, which putatively compensates for the shorter cover-neck bundle of Kin-5. Our results indicate that Kin-1 is mechanically optimized for individual cargo transport, whereas Kin-5 does not necessarily maximize its mechanical performance. Its biochemical rates and enhanced force sensitivity may instead be beneficial for operation in a group of motors. Such variations in subdomains would be a strategy for achieving diversity in motility with the conserved motor head.
authors.affiliation: Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Hesse
authors.forename: Miriam
authors.initials: M
authors.lastname: Steiner
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Wohlever
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.forename: Wonmuk
authors.initials: W
authors.lastname: Hwang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004331:Drosophila melanogaster / Q000737:chemistry; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D052898:Optical Tweezers; D017434:Protein Structure, Tertiary
chemical_list: D016547:Kinesins