The bipolar assembly domain of the mitotic motor kinesin-5

Açar, Şeyda; Carlson, Donald E.; Budamagunta, Madhu S.; Yarov‐Yarovoy, Vladimir; Correia, John J.; Niñonuevo, Milady R.; Jia, Wenbao; Li, Tao; Leary, Julie A.; Voss, John C.; Evans, James E.; Scholey, Jonathan M.

doi:10.1038/ncomms2348

Cited by 82 publications

(90 citation statements)

References 49 publications

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“…1a) absolutely requires KIF11 52 , which is the only member of the kinesin-5 family in humans 53 . KIF11 is built from two homodimers arranged in an antiparallel manner so that identical pairs of heads project from each end of the tetramer, forming a microtubule cross-linker 52,54,55 . The C-terminal tip of the KIF11 tail also contributes to microtubule binding 56 .…”

Section: Centrosome Separationmentioning

confidence: 99%

Prime movers: the mechanochemistry of mitotic kinesins

Cross

McAinsh

2014

Nat Rev Mol Cell Biol

188

203

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Section: Centrosome Separationmentioning

confidence: 99%

Prime movers: the mechanochemistry of mitotic kinesins

Cross

McAinsh

2014

Nat Rev Mol Cell Biol

188

203

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“…In addition, it has been reported that the Xenopus laevis kinesin-5 Eg5 contains a non-motor MT binding site in its tail (24). Finally, it has been shown that the tail domains of the Drosophila melanogaster kinesin-5 Klp61F are located close enough to the motor domains to interact (25). A curious feature that was found for Klp61F is that the central BASS domain of the tetrameric stalk is constructed such that the two pairs of catalytic heads are rotated by 90°to each other (26).…”

mentioning

confidence: 99%

Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality

Düselder

Fridman²,

Thiede

et al. 2015

Journal of Biological Chemistry

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Background: Single molecules of the kinesin-5 Cin8 were previously demonstrated to be minus-end-directed under highionic-strength conditions. Results: Under high-ionic-strength conditions, Cin8 lacking the tail domain is bidirectional. Conclusion:The tail domain is one of the factors that regulate Cin8 directionality. Significance: An important structural element was identified that regulates the directionality of kinesin-5 motors.

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“…Like K1s, K5s have an N-terminal MD followed by a neck-linker (NL) that connects the MD to the rest of the motor. However, K1s are dimeric, whereas K5 tetramerization is mediated by the coiled-coil that follows the K5 NL and gives rise to a dumbbell-shaped molecule with pairs of MDs at either end (3,4). However, it is not simply the K5 tetrameric structure, with each MD pair taking ATPdriven steps toward the MT plus-ends (5), that is required for its mitotic functions: K5 MDs have specific mechanochemical properties that are matched to their spindle functions (6).…”

mentioning

confidence: 99%

Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family

Goulet

Major

Jun

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Kinesins are responsible for a wide variety of microtubule-based, ATP-dependent functions. Their motor domain drives these activities, but the molecular adaptations that specify these diverse and essential cellular activities are poorly understood. It has been assumed that the first identified kinesin-the transport motor kinesin-1-is the mechanistic paradigm for the entire superfamily, but accumulating evidence suggests otherwise. To address the deficits in our understanding of the molecular basis of functional divergence within the kinesin superfamily, we studied kinesin-5s, which are essential mitotic motors whose inhibition blocks cell division. Using cryo-electron microscopy and determination of structure at subnanometer resolution, we have visualized conformations of microtubule-bound human kinesin-5 motor domain at successive steps in its ATPase cycle. After ATP hydrolysis, nucleotide-dependent conformational changes in the active site are allosterically propagated into rotations of the motor domain and uncurling of the drug-binding loop L5. In addition, the mechanical neck-linker element that is crucial for motor stepping undergoes discrete, ordered displacements. We also observed large reorientations of the motor N terminus that indicate its importance for kinesin-5 function through control of neck-linker conformation. A kinesin-5 mutant lacking this N terminus is enzymatically active, and ATP-dependent neck-linker movement and motility are defective, although not ablated. All these aspects of kinesin-5 mechanochemistry are distinct from kinesin-1. Our findings directly demonstrate the regulatory role of the kinesin-5 N terminus in collaboration with the motor's structured neck-linker and highlight the multiple adaptations within kinesin motor domains that tune their mechanochemistries according to distinct functional requirements. molecular motors | macromolecular assemblies | mitosis | cancer N ucleotide triphosphates are the fuel that powers the cell's machinery. Conversion of this fuel into mechanical work, i.e., mechanochemistry, depends on individual machines and the functional context in which they have evolved. Indeed, elucidation of the mechanochemistry of a particular machine provides critical insight into both its functions and modes of regulation. Kinesins are a superfamily of motors that use ATP to undertake microtubule (MT)-based work. Kinesins operate throughout the cell cycle in many contexts and can generate force toward the MT plus or minus end and also depolymerize MTs (1). The kinesin mechanochemical engine-the motor domain (MD)-is highly conserved, and conformational changes in the active site during the motor's ATPase cycle are transmitted to other parts of the MD to generate force (2). Most of our current knowledge about kinesin mechanochemistry comes from studies of the superfamily founding member, the transport motor kinesin-1 (K1) (2). However, accumulating evidence suggests that small modifications within kinesin MDs have profound effects on their cellular function. The molecul...

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The bipolar assembly domain of the mitotic motor kinesin-5

Cited by 82 publications

References 49 publications

Prime movers: the mechanochemistry of mitotic kinesins

Prime movers: the mechanochemistry of mitotic kinesins

Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality

Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family

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