+Open data
-Basic information
Entry | Database: PDB / ID: 8pqz | ||||||||||||
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Title | Cytoplasmic dynein-1 A1/A2 motor domains bound to LIS1 | ||||||||||||
Components |
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Keywords | MOTOR PROTEIN / Dynein / AAA-Atpase / LIS1 | ||||||||||||
Function / homology | Function and homology information corpus callosum morphogenesis / 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 / maintenance of centrosome location / microtubule sliding / Regulation of PLK1 Activity at G2/M Transition / Loss of Nlp from mitotic centrosomes ...corpus callosum morphogenesis / 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 / maintenance of centrosome location / microtubule sliding / 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 / microtubule organizing center organization / platelet activating factor metabolic process / transport along microtubule / acrosome assembly / radial glia-guided pyramidal neuron migration / cerebral cortex neuron differentiation / positive regulation of intracellular transport / dynein light chain binding / central region of growth cone / positive regulation of embryonic development / regulation of metaphase plate congression / establishment of centrosome localization / reelin-mediated signaling pathway / positive regulation of cytokine-mediated signaling pathway / cortical microtubule organization / dynein heavy chain binding / establishment of spindle localization / astral microtubule / positive regulation of spindle assembly / nuclear membrane disassembly / layer formation in cerebral cortex / auditory receptor cell development / vesicle transport along microtubule / stem cell division / positive regulation of dendritic spine morphogenesis / stereocilium / myeloid leukocyte migration / dynein complex / COPI-independent Golgi-to-ER retrograde traffic / minus-end-directed microtubule motor activity / microtubule plus-end binding / negative regulation of JNK cascade / osteoclast development / retrograde axonal transport / dynein light intermediate chain binding / cytoplasmic dynein complex / P-body assembly / brain morphogenesis / motile cilium / nuclear migration / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / microtubule associated complex / COPI-mediated anterograde transport / microtubule motor activity / kinesin complex / dynein intermediate chain binding / cochlea development / dynein complex binding / microtubule-based movement / cytoplasmic microtubule / transmission of nerve impulse / cell leading edge / establishment of mitotic spindle orientation / germ cell development / dynactin binding / phospholipase binding / microtubule-based process / neuromuscular process controlling balance / protein secretion / neuroblast proliferation / positive regulation of axon extension / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / COPI-mediated anterograde transport / regulation of microtubule cytoskeleton organization / lipid catabolic process / cytoplasmic microtubule organization / stress granule assembly / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / JNK cascade / regulation of mitotic spindle organization / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / axon cytoplasm / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / Resolution of Sister Chromatid Cohesion / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / centriole / AURKA Activation by TPX2 / positive regulation of mitotic cell cycle / mitotic spindle organization Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Sus scrofa (pig) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.5 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 | 8pqz.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8pqz.ent.gz | 772.1 KB | Display | PDB format |
PDBx/mmJSON format | 8pqz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8pqz_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
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Full document | 8pqz_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 8pqz_validation.xml.gz | 153.9 KB | Display | |
Data in CIF | 8pqz_validation.cif.gz | 262.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pq/8pqz ftp://data.pdbj.org/pub/pdb/validation_reports/pq/8pqz | HTTPS FTP |
-Related structure data
Related structure data | 17829MC 8pqvC 8pqwC 8pqyC 8pr0C 8pr1C 8pr2C 8pr3C 8pr4C 8pr5C 8ptkC 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
-Cytoplasmic dynein 1 ... , 2 types, 4 molecules AJHI
#1: Protein | Mass: 533055.125 Da / Num. of mol.: 2 / 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 #4: Protein | Mass: 68442.141 Da / Num. of mol.: 2 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 |
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-Protein , 2 types, 8 molecules BCDEKLFG
#2: Protein | Mass: 46709.984 Da / Num. of mol.: 6 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 #3: Protein | Mass: 142015.484 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / References: UniProt: A0A287B8J2 |
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-Non-polymers , 3 types, 12 molecules
#5: Chemical | ChemComp-ADP / #6: Chemical | ChemComp-MG / #7: Chemical | |
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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 | Name: Cytoplasmic dynein-A1/A2 motor domains bound to LIS1 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
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: 5.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 31898 / Symmetry type: POINT | ||||||||||||
Atomic model building | PDB-ID: 7Z8G Accession code: 7Z8G / Source name: PDB / Type: experimental model |