+Open data
-Basic information
Entry | Database: PDB / ID: 7rsq | ||||||||||||||||||
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Title | Cryo-EM structure of KIFBP core | ||||||||||||||||||
Components | KIF-binding protein | ||||||||||||||||||
Keywords | MOTOR PROTEIN / kinesin regulation protein | ||||||||||||||||||
Function / homology | Function and homology information central nervous system projection neuron axonogenesis / mitochondrial transport / kinesin binding / neuron projection maintenance / microtubule cytoskeleton organization / in utero embryonic development / cytoskeleton / mitochondrion Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||||||||
Model details | MODEL GENERATED BY ROSETTA VERSION 2020.08+release.cb1caba | ||||||||||||||||||
Authors | Solon, A.L. / Tan, Z. / Schutt, K.L. / Jepsen, L. / Haynes, S.E. / Nesvizhskii, A.I. / Sept, D. / Stumpff, J. / Ohi, R. / Cianfrocco, M.A. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: Sci Adv / Year: 2021 Title: Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding. Authors: April L Solon / Zhenyu Tan / Katherine L Schutt / Lauren Jepsen / Sarah E Haynes / Alexey I Nesvizhskii / David Sept / Jason Stumpff / Ryoma Ohi / Michael A Cianfrocco / Abstract: Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits ...Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits the catalytic motor heads of 8 of 45 kinesin superfamily members, but the mechanism remains poorly defined. Here, we used cryo–electron microscopy and cross-linking mass spectrometry to determine high-resolution structures of KIFBP alone and in complex with two mitotic kinesins, revealing structural remodeling of kinesin by KIFBP. We find that KIFBP remodels kinesin motors and blocks microtubule binding (i) via allosteric changes to kinesin and (ii) by sterically blocking access to the microtubule. We identified two regions of KIFBP necessary for kinesin binding and cellular regulation during mitosis. Together, this work further elucidates the molecular mechanism of KIFBP-mediated kinesin inhibition and supports a model in which structural rearrangement of kinesin motor domains by KIFBP abrogates motor protein activity. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7rsq.cif.gz | 98.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rsq.ent.gz | 70.8 KB | Display | PDB format |
PDBx/mmJSON format | 7rsq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rs/7rsq ftp://data.pdbj.org/pub/pdb/validation_reports/rs/7rsq | HTTPS FTP |
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-Related structure data
Related structure data | 24677MC 7rsiC 7rypC 7ryqC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 71913.945 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KIFBP, KBP, KIAA1279, KIF1BP / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q96EK5 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: high-resolution structure of KIFBP(core) / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.7 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Particle selection | Num. of particles selected: 128190 | |||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 128190 / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |