+Open data
-Basic information
Entry | Database: PDB / ID: 8pqy | ||||||||||||
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Title | Cytoplasmic dynein-1 motor domain bound to LIS1 | ||||||||||||
Components |
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Keywords | MOTOR PROTEIN / Dynein / AAA-Atpase / p150 / 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 / platelet activating factor metabolic process / acrosome assembly ...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 / platelet activating factor metabolic process / acrosome assembly / radial glia-guided pyramidal neuron migration / microtubule organizing center organization / cerebral cortex neuron differentiation / 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 / positive regulation of cytokine-mediated signaling pathway / cortical microtubule organization / establishment of spindle localization / astral microtubule / positive regulation of spindle assembly / layer formation in cerebral cortex / nuclear membrane disassembly / auditory receptor cell development / positive regulation of dendritic spine morphogenesis / vesicle transport along microtubule / stem cell division / stereocilium / P-body assembly / myeloid leukocyte migration / dynein complex / COPI-independent Golgi-to-ER retrograde traffic / microtubule plus-end binding / minus-end-directed microtubule motor activity / cytoplasmic dynein complex / negative regulation of JNK cascade / retrograde axonal transport / dynein light intermediate chain binding / brain morphogenesis / motile cilium / nuclear migration / osteoclast development / microtubule associated complex / kinesin complex / dynein intermediate chain binding / dynein complex binding / cochlea development / transmission of nerve impulse / cell leading edge / germ cell development / dynactin binding / establishment of mitotic spindle orientation / phospholipase binding / neuromuscular process controlling balance / neuroblast proliferation / protein secretion / positive regulation of axon extension / cytoplasmic microtubule / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / microtubule-based process / COPI-mediated anterograde transport / lipid catabolic process / regulation of microtubule cytoskeleton organization / stress granule assembly / cytoplasmic microtubule organization / Mitotic Prometaphase / regulation of mitotic spindle organization / EML4 and NUDC in mitotic spindle formation / axon cytoplasm / JNK cascade / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Resolution of Sister Chromatid Cohesion / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / Anchoring of the basal body to the plasma membrane / MHC class II antigen presentation / positive regulation of mitotic cell cycle / adult locomotory behavior / AURKA Activation by TPX2 / mitotic spindle organization / filopodium / RHO GTPases Activate Formins / hippocampus development / phosphoprotein binding / neuron migration / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / cerebral cortex development / microtubule cytoskeleton organization / kinetochore / Aggrephagy / HCMV Early Events / Separation of Sister Chromatids / azurophil granule lumen / Regulation of PLK1 Activity at G2/M Transition Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 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 | 8pqy.cif.gz | 662.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8pqy.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8pqy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pq/8pqy ftp://data.pdbj.org/pub/pdb/validation_reports/pq/8pqy | HTTPS FTP |
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-Related structure data
Related structure data | 17828MC 8pqvC 8pqwC 8pqzC 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
#1: Protein | Mass: 533055.125 Da / Num. of mol.: 1 / 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 | ||||||||
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#2: Protein | Mass: 46709.984 Da / Num. of mol.: 2 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: Chemical | #4: Chemical | #5: Chemical | ChemComp-ATP / | Has ligand of interest | Y | |
-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-1 bound to LIS1 / Type: COMPLEX / Entity ID: #1-#2 / 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 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 | Name: PHENIX / Version: 1.20_4459: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 90594 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7Z8G Accession code: 7Z8G / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
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