A Second Tubulin Binding Site on the Kinesin-13 Motor Head Domain Is Important during Mitosis

Zhang, Dong; Asenjo, Ana B.; Greenbaum, Michaela; Xie, Luping; Sharp, David J.; Sosa, Hernando

doi:10.1371/journal.pone.0073075

Cited by 20 publications

(22 citation statements)

References 58 publications

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“…With improved coverage, we observed that MCAK is strongly stabilized when captured in an intermediate state of depolymerization. This is consistent with a two-site tubulin binding mode previously reported (Zhang et al, 2013). Our analysis also supports an outwardly curving protofilament geometry: the tubulin surface normally within the lumen of a microtubule is now exposed (Figure 5B).…”

Section: Resultssupporting

confidence: 93%

Mass Spec Studio for Integrative Structural Biology

et al. 2014

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SUMMARY The integration of biophysical data from multiple sources is critical for developing accurate structural models of large multiprotein systems and their regulators. Mass spectrometry (MS) can be used to measure the insertion location for a wide range of topographically sensitive chemical probes, and such insertion data provide a rich, but disparate set of modeling restraints. We have developed a software platform that integrates the analysis of label-based MS data with protein modeling activities (Mass Spec Studio). Analysis packages can mine any labeling data from any mass spectrometer in a proteomics-grade manner, and link labeling methods with data-directed protein interaction modeling using HADDOCK. Support is provided for hydrogen/ deuterium exchange (HX) and covalent labeling chemistries, including novel acquisition strategies such as targeted HX-tandem MS (MS2) and data-independent HX-MS2. The latter permits the modeling of highly complex systems, which we demonstrate by the analysis of microtubule interactions.

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Section: Resultssupporting

confidence: 93%

Mass Spec Studio for Integrative Structural Biology

et al. 2014

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“…This behavior of the Ska1 MTBD is strikingly similar to that observed for the kinesin-13 MCAK, which also induces the formation of a protofilament-like structure encircling microtubules [4–6]. In the case of both Ska1 and MCAK, it is unlikely that such a spiral or ring-like assembly is formed in cells (as occurs for the fungal Dam1 complex, for example [7, 8]).…”

Section: Resultssupporting

confidence: 64%

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

et al. 2017

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Summary The macromolecular kinetochore functions to generate interactions between chromosomal DNA and spindle microtubules [1]. To facilitate chromosome movement and segregation, kinetochores must maintain associations with both growing and shrinking microtubule ends. It is critical to define the proteins and their properties that allow kinetochores to associate with dynamic microtubules. The kinetochore-localized human Ska1 complex binds to microtubules and tracks with depolymerizing microtubule ends [2]. We now demonstrate that the Ska1 complex also autonomously tracks with growing microtubule ends in vitro, a key property that would allow this complex to act at kinetochores to mediate persistent associations with dynamic microtubules. To define the basis for Ska1 complex interactions with dynamic microtubules, we investigated the tubulin-binding properties of the Ska1 microtubule binding domain. In addition to binding to the microtubule lattice and dolastatin-induced protofilament-like structures, we demonstrate that the Ska1 microtubule binding domain can associate with soluble tubulin heterodimers and promote assembly of oligomeric ring-like tubulin structures. We generated mutations on distinct surfaces of the Ska1 microtubule binding domain that disrupt binding to soluble tubulin, but do not prevent microtubule binding. These mutants display compromised microtubule tracking activity in vitro and result in defective chromosome alignment and mitotic progression in cells using a CRISPR/Cas9-based replacement assay. Our work supports a model in which multiple surfaces of Ska1 interact with diverse tubulin substrates to associate with dynamic microtubule polymers and facilitate optimal chromosome segregation.

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“…While both kinesin-8s and kinesin-13s also bind microtubules outside of their canonical motor domains, these kinesins still require ATP hydrolysis to affect microtubule dynamics. The secondary microtubule binding site of kinesin-13 is nucleotide-independent, but this kinesin still utilizes the hydrolysis of ATP to destabilize microtubules (Zhang et al, 2013), while the kinesin-8 Kip3 can either stabilize or destabilize microtubules through discrete binding sites in the motor domain (Fukuda et al, 2014; Su et al, 2011). In contrast, the C-terminal dependent tethering of KIF21B to microtubules is completely sufficient for regulation of dynamic instability, independent of motor function or ATP hydrolysis.…”

Section: Discussionmentioning

confidence: 99%

Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B

Ghiretti

Thies

Tokito

et al. 2016

Neuron

137

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Summary The dendritic arbor is subject to continual activity-dependent remodeling, requiring a balance between directed cargo trafficking and dynamic restructuring of the underlying microtubule tracks. How cytoskeletal components are able to dynamically regulate these processes to maintain this balance remains largely unknown. By combining single molecule assays and live imaging in rat hippocampal neurons, we have identified the kinesin-4 KIF21B as a molecular regulator of activity-dependent trafficking and microtubule dynamicity in dendrites. We find that KIF21B contributes to the retrograde trafficking of BDNF/TrkB complexes, and also regulates microtubule dynamics through a separable, non-motor microtubule-binding domain. Neuronal activity enhances the motility of KIF21B at the expense of its role in cytoskeletal remodeling, the first example of a kinesin whose function is directly tuned to neuronal activity state. These studies suggest a model in which KIF21B navigates the complex cytoskeletal environment of dendrites by compartmentalizing functions in an activity-dependent manner.

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A Second Tubulin Binding Site on the Kinesin-13 Motor Head Domain Is Important during Mitosis

Cited by 20 publications

References 58 publications

Mass Spec Studio for Integrative Structural Biology

Mass Spec Studio for Integrative Structural Biology

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B

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