+Open data
-Basic information
Entry | Database: PDB / ID: 8ptk | ||||||||||||
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Title | Composite structure of Dynein-Dynactin-JIP3-LIS1 | ||||||||||||
Components |
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Keywords | MOTOR PROTEIN / Dynein / AAA-Atpase / p150 / LIS1 / Dynactin / JIP3 | ||||||||||||
Function / homology | Function and homology information Regulation of PLK1 Activity at G2/M Transition / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / intracellular transport of viral protein in host cell / corpus callosum morphogenesis / secretory vesicle / establishment of planar polarity of embryonic epithelium ...Regulation of PLK1 Activity at G2/M Transition / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / intracellular transport of viral protein in host cell / corpus callosum morphogenesis / secretory vesicle / establishment of planar polarity of embryonic epithelium / microtubule cytoskeleton organization involved in establishment of planar polarity / ameboidal-type cell migration / interneuron migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / positive regulation of neuromuscular junction development / retrograde axonal transport of mitochondrion / centriolar subdistal appendage / Gap junction degradation / Formation of annular gap junctions / Regulation of actin dynamics for phagocytic cup formation / EPHB-mediated forward signaling / VEGFA-VEGFR2 Pathway / Cell-extracellular matrix interactions / RHO GTPases Activate WASPs and WAVEs / MAP2K and MAPK activation / maintenance of centrosome location / microtubule sliding / dynactin complex / positive regulation of non-motile cilium assembly / Clathrin-mediated endocytosis / centriole-centriole cohesion / transport along microtubule / intraciliary retrograde transport / visual behavior / platelet activating factor metabolic process / dynein light chain binding / ventral spinal cord development / microtubule anchoring at centrosome / WASH complex / acrosome assembly / radial glia-guided pyramidal neuron migration / microtubule organizing center organization / F-actin capping protein complex / cerebral cortex neuron differentiation / mitocytosis / motile cilium assembly / dynein heavy chain binding / negative regulation of filopodium assembly / central region of growth cone / positive regulation of intracellular transport / positive regulation of embryonic development / reelin-mediated signaling pathway / regulation of metaphase plate congression / establishment of centrosome localization / anterograde axonal protein transport / positive regulation of cytokine-mediated signaling pathway / cortical microtubule organization / cellular response to cytochalasin B / establishment of spindle localization / Activation of BIM and translocation to mitochondria / melanosome transport / astral microtubule / cytoskeleton-dependent cytokinesis / ciliary tip / positive regulation of spindle assembly / layer formation in cerebral cortex / regulation of transepithelial transport / retromer complex / nuclear membrane disassembly / structural constituent of postsynaptic actin cytoskeleton / auditory receptor cell development / morphogenesis of a polarized epithelium / microtubule plus-end / positive regulation of dendritic spine morphogenesis / vesicle transport along microtubule / positive regulation of microtubule nucleation / Intraflagellar transport / postsynaptic actin cytoskeleton / protein localization to adherens junction / dense body / Tat protein binding / stem cell division / negative regulation of nitric oxide biosynthetic process / Neutrophil degranulation / MAP-kinase scaffold activity / stereocilium / negative regulation of phosphorylation / P-body assembly / myeloid leukocyte migration / dynein complex / COPI-independent Golgi-to-ER retrograde traffic / regulation of G protein-coupled receptor signaling pathway / apical protein localization / microtubule plus-end binding / microtubule-dependent intracellular transport of viral material towards nucleus / minus-end-directed microtubule motor activity / barbed-end actin filament capping / cytoplasmic dynein complex / JUN kinase binding / negative regulation of JNK cascade Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Sus scrofa (pig) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 10 Å | ||||||||||||
Authors | Singh, K. / Lau, C.K. / Manigrasso, G. / Gassmann, R. / Carter, A.P. | ||||||||||||
Funding support | United Kingdom, European Union, 3items
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Citation | Journal: Science / Year: 2024 Title: Molecular mechanism of dynein-dynactin complex assembly by LIS1. Authors: Kashish Singh / Clinton K Lau / Giulia Manigrasso / José B Gama / Reto Gassmann / Andrew P Carter / Abstract: Cytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as a ~4-megadalton complex containing its cofactor dynactin and a cargo-specific coiled-coil ...Cytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as a ~4-megadalton complex containing its cofactor dynactin and a cargo-specific coiled-coil adaptor. However, how dynein and dynactin recognize diverse adaptors, how they interact with each other during complex formation, and the role of critical regulators such as lissencephaly-1 (LIS1) protein (LIS1) remain unclear. In this study, we determined the cryo-electron microscopy structure of dynein-dynactin on microtubules with LIS1 and the lysosomal adaptor JIP3. This structure reveals the molecular basis of interactions occurring during dynein activation. We show how JIP3 activates dynein despite its atypical architecture. Unexpectedly, LIS1 binds dynactin's p150 subunit, tethering it along the length of dynein. Our data suggest that LIS1 and p150 constrain dynein-dynactin to ensure efficient complex formation. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ptk.cif.gz | 4.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8ptk.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ptk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pt/8ptk ftp://data.pdbj.org/pub/pdb/validation_reports/pt/8ptk | HTTPS FTP |
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-Related structure data
Related structure data | 17873MC 8pqvC 8pqwC 8pqyC 8pqzC 8pr0C 8pr1C 8pr2C 8pr3C 8pr4C 8pr5C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 8 types, 19 molecules 1234ABCDEFGIHJKLUXx
#1: Protein | Mass: 46709.984 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PAFAH1B1, LIS1, MDCR, MDS, PAFAHA / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P43034 #2: Protein | Mass: 42670.688 Da / Num. of mol.: 8 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: F2Z5G5 #3: Protein | | Mass: 41782.660 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: Q6QAQ1 #4: Protein | | Mass: 46250.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: I3LHK5 #5: Protein | | Mass: 33059.848 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0PFK5 #6: Protein | | Mass: 30669.768 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0PFK7 #10: Protein | | Mass: 20703.910 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: D0G6S1 #12: Protein | Mass: 65975.398 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK8IP3, JIP3, KIAA1066 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9UPT6 |
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-Dynactin subunit ... , 5 types, 10 molecules MNPQORSTWY
#7: Protein | Mass: 44704.414 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0A5G2QD80 #8: Protein | Mass: 21192.477 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: F1SEC0 #9: Protein | Mass: 142015.484 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0A287B8J2 #11: Protein | | Mass: 20150.533 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0A286ZK88 #13: Protein | | Mass: 52920.434 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0A4X1TB62 |
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-Dynein light chain ... , 3 types, 12 molecules abdiklvystwz
#14: Protein | Mass: 10381.899 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNLL1, DLC1, DNCL1, DNCLC1, HDLC1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63167 #18: Protein | Mass: 12461.996 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNLT1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63172 #19: Protein | Mass: 10934.576 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNLRB1, BITH, DNCL2A, DNLC2A, ROBLD1, HSPC162 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NP97 |
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-Cytoplasmic dynein 1 ... , 3 types, 12 molecules efmnghopjqru
#15: Protein | Mass: 533055.125 Da / Num. of mol.: 4 / Mutation: R1567E, K1610E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNC1H1, DHC1, DNCH1, DNCL, DNECL, DYHC, KIAA0325 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14204 #16: Protein | Mass: 68442.141 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNC1I2, DNCI2, DNCIC2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q13409 #17: Protein | Mass: 54173.156 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYNC1LI2, DNCLI2, LIC2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O43237 |
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-Non-polymers , 5 types, 35 molecules
#20: Chemical | ChemComp-ADP / #21: Chemical | ChemComp-ATP / #22: Chemical | #23: Chemical | ChemComp-MG / #24: Chemical | ChemComp-ANP / |
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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: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | ||||||||||||||||||||||||
Buffer solution | pH: 7.2 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 4000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 53 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3D reconstruction | Resolution: 10 Å / Resolution method: OTHER / Num. of particles: 700290 / Symmetry type: POINT | ||||||||||||
Atomic model building | PDB-ID: 7Z8G Accession code: 7Z8G / Source name: PDB / Type: experimental model |