+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24672 | |||||||||||||||
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Title | The cryo-EM map of KIF18A bound to KIFBP | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Function / homology | Function and homology information tubulin-dependent ATPase activity / mitotic spindle astral microtubule / mitotic spindle midzone / central nervous system projection neuron axonogenesis / kinetochore microtubule / male meiotic nuclear division / microtubule plus-end binding / Kinesins / plus-end-directed microtubule motor activity / COPI-dependent Golgi-to-ER retrograde traffic ...tubulin-dependent ATPase activity / mitotic spindle astral microtubule / mitotic spindle midzone / central nervous system projection neuron axonogenesis / kinetochore microtubule / male meiotic nuclear division / microtubule plus-end binding / Kinesins / plus-end-directed microtubule motor activity / COPI-dependent Golgi-to-ER retrograde traffic / microtubule depolymerization / kinesin complex / mitotic metaphase chromosome alignment / mitochondrial transport / microtubule-based movement / seminiferous tubule development / mitotic sister chromatid segregation / kinesin binding / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / regulation of microtubule cytoskeleton organization / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / ruffle / Resolution of Sister Chromatid Cohesion / MHC class II antigen presentation / neuron projection maintenance / cellular response to estradiol stimulus / caveola / RHO GTPases Activate Formins / microtubule cytoskeleton organization / kinetochore / Separation of Sister Chromatids / microtubule cytoskeleton / protein transport / actin binding / microtubule binding / in utero embryonic development / cytoskeleton / centrosome / ATP hydrolysis activity / mitochondrion / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.9 Å | |||||||||||||||
Authors | Tan Z / Solon AL / Schutt KL / Jepsen L / Haynes SE / Nesvizhskii AI / Sept D / Stumpff J / Ohi R / Cianfrocco MA | |||||||||||||||
Funding support | United States, 4 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_24672.map.gz | 96.9 MB | EMDB map data format | |
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Header (meta data) | emd-24672-v30.xml emd-24672.xml | 20 KB 20 KB | Display Display | EMDB header |
Images | emd_24672.png | 35.2 KB | ||
Masks | emd_24672_msk_1.map | 103 MB | Mask map | |
Others | emd_24672_additional_1.map.gz emd_24672_half_map_1.map.gz emd_24672_half_map_2.map.gz | 50.9 MB 95.6 MB 95.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24672 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24672 | HTTPS FTP |
-Related structure data
Related structure data | 7rsiMC 7rsqC 7rypC 7ryqC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_24672.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 0.91 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_24672_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: unsharpened map
File | emd_24672_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_24672_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_24672_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : KIFBP:KIF18A complex
Entire | Name: KIFBP:KIF18A complex |
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Components |
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-Supramolecule #1: KIFBP:KIF18A complex
Supramolecule | Name: KIFBP:KIF18A complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: KIF-binding protein
Macromolecule | Name: KIF-binding protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 71.913945 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MANVPWAEVC EKFQAALALS RVELHKNPEK EPYKSKYSAR ALLEEVKALL GPAPEDEDER PEAEDGPGAG DHALGLPAEV VEPEGPVAQ RAVRLAVIEF HLGVNHIDTE ELSAGEEHLV KCLRLLRRYR LSHDCISLCI QAQNNLGILW SEREEIETAQ A YLESSEAL ...String: MANVPWAEVC EKFQAALALS RVELHKNPEK EPYKSKYSAR ALLEEVKALL GPAPEDEDER PEAEDGPGAG DHALGLPAEV VEPEGPVAQ RAVRLAVIEF HLGVNHIDTE ELSAGEEHLV KCLRLLRRYR LSHDCISLCI QAQNNLGILW SEREEIETAQ A YLESSEAL YNQYMKEVGS PPLDPTERFL PEEEKLTEQE RSKRFEKVYT HNLYYLAQVY QHLEMFEKAA HYCHSTLKRQ LE HNAYHPI EWAINAATLS QFYINKLCFM EARHCLSAAN VIFGQTGKIS ATEDTPEAEG EVPELYHQRK GEIARCWIKY CLT LMQNAQ LSMQDNIGEL DLDKQSELRA LRKKELDEEE SIRKKAVQFG TGELCDAISA VEEKVSYLRP LDFEEARELF LLGQ HYVFE AKEFFQIDGY VTDHIEVVQD HSALFKVLAF FETDMERRCK MHKRRIAMLE PLTVDLNPQY YLLVNRQIQF EIAHA YYDM MDLKVAIADR LRDPDSHIVK KINNLNKSAL KYYQLFLDSL RDPNKVFPEH IGEDVLRPAM LAKFRVARLY GKIITA DPK KELENLATSL EHYKFIVDYC EKHPEAAQEI EVELELSKEM VSLLPTKMER FRTKMALT |
-Macromolecule #2: Kinesin-like protein KIF18A
Macromolecule | Name: Kinesin-like protein KIF18A / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 39.560008 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MSVTEEDLCH HMKVVVRVRP ENTKEKAAGF HKVVHVVDKH ILVFDPKQEE VSFFHGKKTT NQNVIKKQNK DLKFVFDAVF DETSTQSEV FEHTTKPILR SFLNGYNCTV LAYGATGAGK THTMLGSADE PGVMYLTMLH LYKCMDEIKE EKICSTAVSY L EVYNEQIR ...String: MSVTEEDLCH HMKVVVRVRP ENTKEKAAGF HKVVHVVDKH ILVFDPKQEE VSFFHGKKTT NQNVIKKQNK DLKFVFDAVF DETSTQSEV FEHTTKPILR SFLNGYNCTV LAYGATGAGK THTMLGSADE PGVMYLTMLH LYKCMDEIKE EKICSTAVSY L EVYNEQIR DLLVNSGPLA VREDTQKGVV VHGLTLHQPK SSEEILHLLD NGNKNRTQHP TDMNATSSRS HAVFQIYLRQ QD KTASINQ NVRIAKMSLI DLAGSERAST SGAKGTRFVE GTNINRSLLA LGNVINALAD SKRKNQHIPY RNSKLTRLLK DSL GGNCQT IMIAAVSPSS VFYDDTYNTL KYANRAK |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.5 mg/mL |
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Buffer | pH: 7.7 |
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: cryosparc ab-initio |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Details: cryosparc |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Details: cryosparc |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 54801 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | PDB-7rsi: |