title: Secondary structure and compliance of a predicted flexible domain in kinesin-1 necessary for cooperation of motors.
abstract: Although the mechanism by which a kinesin-1 molecule moves individually along a microtubule is quite well-understood, the way that many kinesin-1 motor proteins bound to the same cargo move together along a microtubule is not. We identified a 60-amino-acid-long domain, termed Hinge 1, in kinesin-1 from Drosophila melanogaster that is located between the coiled coils of the neck and stalk domains. Its deletion reduces microtubule gliding speed in multiple-motor assays but not single-motor assays. Hinge 1 thus facilitates the cooperation of motors by preventing them from impeding each other. We addressed the structural basis for this phenomenon. Video-microscopy of single microtubule-bound full-length motors reveals the sporadic occurrence of high-compliance states alternating with longer-lived, low-compliance states. The deletion of Hinge 1 abolishes transitions to the high-compliance state. Based on Fourier transform infrared, circular dichroism, and fluorescence spectroscopy of Hinge 1 peptides, we propose that low-compliance states correspond to an unexpected structured organization of the central Hinge 1 region, whereas high-compliance states correspond to the loss of that structure. We hypothesize that strain accumulated during multiple-kinesin motility populates the high-compliance state by unfolding helical secondary structure in the central Hinge 1 domain flanked by unordered regions, thereby preventing the motors from interfering with each other in multiple-motor situations.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Alvaro H
authors.initials: AH
authors.lastname: Crevenna
authors.forename: Sineej
authors.initials: S
authors.lastname: Madathil
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cohen
authors.forename: Michael
authors.initials: M
authors.lastname: Wagenbach
authors.forename: Karim
authors.initials: K
authors.lastname: Fahmy
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004548:Elasticity; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009068:Movement; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013696:Temperature
chemical_list: D029721:Drosophila Proteins; D010455:Peptides; C515209:Khc protein, Drosophila; D016547:Kinesins
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