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- PDB-6ta3: Human kinesin-5 motor domain in the GSK-1 state bound to microtub... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6ta3 | ||||||||||||
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Title | Human kinesin-5 motor domain in the GSK-1 state bound to microtubules (Conformation 1) | ||||||||||||
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![]() | CELL CYCLE / kinesin / microtubule / mitosis / inhibition / motor | ||||||||||||
Function / homology | ![]() spindle elongation / regulation of mitotic centrosome separation / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III ...spindle elongation / regulation of mitotic centrosome separation / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Aggrephagy / Resolution of Sister Chromatid Cohesion / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Separation of Sister Chromatids / Kinesins / plus-end-directed microtubule motor activity / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins / mitotic centrosome separation / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / COPI-mediated anterograde transport / COPI-dependent Golgi-to-ER retrograde traffic / microtubule motor activity / kinesin complex / spindle organization / microtubule-based movement / mitotic spindle assembly / MHC class II antigen presentation / mitotic spindle organization / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / spindle microtubule / structural constituent of cytoskeleton / mitotic spindle / spindle pole / microtubule cytoskeleton organization / spindle / microtubule cytoskeleton / mitotic cell cycle / microtubule binding / microtubule / cell division / GTPase activity / GTP binding / protein kinase binding / protein-containing complex / ATP binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||
![]() | Pena, A. / Sweeney, A. / Cook, A.D. / Moores, C.A. / Topf, M. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy. Authors: Alejandro Peña / Aaron Sweeney / Alexander D Cook / Julia Locke / Maya Topf / Carolyn A Moores / ![]() Abstract: Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which ...Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric human kinesin-5 ATPase and microtubule gliding activities, and promotes the motor's microtubule stabilization activity. Using cryoelectron microscopy, we determined the 3D structure of the microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The structure reveals that GSK-1 stabilizes the microtubule binding surface of the motor in an ATP-like conformation, while destabilizing regions of the motor around the empty nucleotide binding pocket. Density corresponding to GSK-1 is located between helix-α4 and helix-α6 in the motor domain at its interface with the microtubule. Using a combination of difference mapping and protein-ligand docking, we characterized the kinesin-5-GSK-1 interaction and further validated this binding site using mutagenesis. This work opens up new avenues of investigation of kinesin inhibition and spindle perturbation. #1: ![]() Title: Mechanism of microtubule-trapped human kinesin-5 inhibition revealed using cryo-EM Authors: Pena, A.P. / Sweeney, A. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 220.5 KB | Display | ![]() |
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PDB format | ![]() | 179.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 952.9 KB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 98.1 KB | Display | |
Data in CIF | ![]() | 136.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 10421MC ![]() 6ta4C ![]() 6tiwC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 3 types, 3 molecules BAK
#1: Protein | Mass: 48113.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: Protein | Mass: 48780.117 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: Protein | Mass: 43727.461 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 3 types, 5 molecules ![](data/chem/img/G2P.gif)
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![](data/chem/img/MZK.gif)
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#4: Chemical | #5: Chemical | #6: Chemical | ChemComp-MZK / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.6 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Helical symmerty | Angular rotation/subunit: -25.7 ° / Axial rise/subunit: 8.9 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 507219 / Symmetry type: HELICAL |