+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 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 / nitric-oxide synthase inhibitor activity / ameboidal-type cell migration / interneuron migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / retrograde axonal transport of mitochondrion ...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 / nitric-oxide synthase inhibitor activity / ameboidal-type cell migration / interneuron migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / retrograde axonal transport of mitochondrion / negative regulation of DNA strand resection involved in replication fork processing / Gap junction degradation / Formation of annular gap junctions / Regulation of actin dynamics for phagocytic cup formation / EPHB-mediated forward signaling / Adherens junctions interactions / VEGFA-VEGFR2 Pathway / Cell-extracellular matrix interactions / RHO GTPases Activate WASPs and WAVEs / MAP2K and MAPK activation / UCH proteinases / Clathrin-mediated endocytosis / RHOF GTPase cycle / maintenance of centrosome location / microtubule sliding / dynactin complex / 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 / transport along microtubule / visual behavior / platelet activating factor metabolic process / intraciliary retrograde transport / WASH complex / radial glia-guided pyramidal neuron migration / F-actin capping protein complex / cerebral cortex neuron differentiation / microtubule organizing center organization / positive regulation of intracellular transport / dynein light chain binding / central region of growth cone / acrosome assembly / positive regulation of embryonic development / negative regulation of filopodium assembly / reelin-mediated signaling pathway / regulation of metaphase plate congression / establishment of centrosome localization / anterograde axonal protein transport / positive regulation of cytokine-mediated signaling pathway / motile cilium assembly / cortical microtubule organization / dynein heavy chain binding / establishment of spindle localization / Activation of BIM and translocation to mitochondria / astral microtubule / axonemal dynein complex / positive regulation of spindle assembly / nuclear membrane disassembly / ciliary tip / cytoskeleton-dependent cytokinesis / layer formation in cerebral cortex / cell tip / auditory receptor cell development / structural constituent of postsynaptic actin cytoskeleton / vesicle transport along microtubule / positive regulation of dendritic spine morphogenesis / microtubule plus-end / dense body / Intraflagellar transport / stem cell division / negative regulation of nitric oxide biosynthetic process / MAP-kinase scaffold activity / stereocilium / myeloid leukocyte migration / dynein complex / regulation of G protein-coupled receptor signaling pathway / negative regulation of phosphorylation / Neutrophil degranulation / P-body assembly / COPI-independent Golgi-to-ER retrograde traffic / negative regulation of JNK cascade / microtubule-dependent intracellular transport of viral material towards nucleus / minus-end-directed microtubule motor activity / JUN kinase binding / barbed-end actin filament capping / dynein light intermediate chain binding / microtubule plus-end binding / cytoplasmic dynein complex / brain morphogenesis / regulation of cell morphogenesis / motile cilium / regulation of lamellipodium assembly / retrograde axonal transport / enzyme inhibitor activity / nuclear migration / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins 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
Summary document | 8ptk_validation.pdf.gz | 2.4 MB | Display | wwPDB validaton report |
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Full document | 8ptk_full_validation.pdf.gz | 2.4 MB | Display | |
Data in XML | 8ptk_validation.xml.gz | 548.4 KB | Display | |
Data in CIF | 8ptk_validation.cif.gz | 987.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pt/8ptk ftp://data.pdbj.org/pub/pdb/validation_reports/pt/8ptk | HTTPS FTP |
-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 FIELD / 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 |