+Open data
-Basic information
Entry | Database: PDB / ID: 8dyv | |||||||||
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Title | Structure of human cytoplasmic dynein-1 bound to one Lis1 | |||||||||
Components |
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Keywords | MOTOR PROTEIN / dynein / transport | |||||||||
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 / 1-alkyl-2-acetylglycerophosphocholine esterase complex / interneuron migration / maintenance of centrosome location / microtubule sliding / platelet activating factor metabolic process / microtubule organizing center organization ...corpus callosum morphogenesis / establishment of planar polarity of embryonic epithelium / microtubule cytoskeleton organization involved in establishment of planar polarity / ameboidal-type cell migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / interneuron migration / maintenance of centrosome location / microtubule sliding / platelet activating factor metabolic process / microtubule organizing center organization / acrosome assembly / radial glia-guided pyramidal neuron migration / cerebral cortex neuron differentiation / positive regulation of intracellular transport / central region of growth cone / regulation of metaphase plate congression / establishment of centrosome localization / positive regulation of embryonic development / positive regulation of cytokine-mediated signaling pathway / cortical microtubule organization / establishment of spindle localization / astral microtubule / reelin-mediated signaling pathway / 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 / minus-end-directed microtubule motor activity / COPI-independent Golgi-to-ER retrograde traffic / osteoclast development / microtubule plus-end binding / negative regulation of JNK cascade / retrograde axonal transport / cytoplasmic dynein complex / dynein light intermediate chain binding / P-body assembly / brain morphogenesis / motile cilium / nuclear migration / microtubule associated complex / kinesin complex / dynein intermediate chain binding / cochlea development / dynein complex binding / cell leading edge / cytoplasmic microtubule / transmission of nerve impulse / establishment of mitotic spindle orientation / germ cell development / phospholipase binding / dynactin binding / microtubule-based process / neuromuscular process controlling balance / neuroblast proliferation / protein secretion / positive regulation of axon extension / COPI-mediated anterograde transport / regulation of microtubule cytoskeleton organization / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / lipid catabolic process / cytoplasmic microtubule organization / stress granule assembly / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / JNK cascade / regulation of mitotic spindle organization / Recruitment of mitotic centrosome proteins and complexes / axon cytoplasm / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / Resolution of Sister Chromatid Cohesion / AURKA Activation by TPX2 / positive regulation of mitotic cell cycle / mitotic spindle organization / adult locomotory behavior / filopodium / hippocampus development / RHO GTPases Activate Formins / phosphoprotein binding / neuron migration / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / cerebral cortex development / kinetochore / microtubule cytoskeleton organization / 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: 3.97 Å | |||||||||
Authors | Reimer, J.M. / DeSantis, M. / Reck-Peterson, S.L. / Leschziner, A.E. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Elife / Year: 2023 Title: Structures of human dynein in complex with the lissencephaly 1 protein, LIS1. Authors: Janice M Reimer / Morgan E DeSantis / Samara L Reck-Peterson / Andres E Leschziner / Abstract: The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by ...The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by relieving its autoinhibited form. Previously we reported a 3.1 Å structure of yeast dynein bound to Pac1, the yeast homologue of LIS1, which revealed the details of their interactions (Gillies et al., 2022). Based on this structure, we made mutations that disrupted these interactions and showed that they were required for dynein's function in vivo in yeast. We also used our yeast dynein-Pac1 structure to design mutations in human dynein to probe the role of LIS1 in promoting the assembly of active dynein complexes. These mutations had relatively mild effects on dynein activation, suggesting that there may be differences in how dynein and Pac1/LIS1 interact between yeast and humans. Here, we report cryo-EM structures of human dynein-LIS1 complexes. Our new structures reveal the differences between the yeast and human systems, provide a blueprint to disrupt the human dynein-LIS1 interactions more accurately, and map type-1 lissencephaly disease mutations, as well as mutations in dynein linked to malformations of cortical development/intellectual disability, in the context of the dynein-LIS1 complex. #1: Journal: Elife / Year: 2022 Title: Structural basis for cytoplasmic dynein-1 regulation by Lis1. Authors: Gillies, J.P. / Reimer, J.M. / Karasmanis, E.P. / Lahiri, I. / Htet, Z.M. / Leschziner, A.E. / Reck-Peterson, S.L. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dyv.cif.gz | 1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8dyv.ent.gz | 878 KB | Display | PDB format |
PDBx/mmJSON format | 8dyv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dyv_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8dyv_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8dyv_validation.xml.gz | 87.8 KB | Display | |
Data in CIF | 8dyv_validation.cif.gz | 133.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dy/8dyv ftp://data.pdbj.org/pub/pdb/validation_reports/dy/8dyv | HTTPS FTP |
-Related structure data
Related structure data | 27783MC 8dyuC 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: 380953.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14204 | ||||
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#2: Protein | Mass: 46722.918 Da / Num. of mol.: 1 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 | ChemComp-ATP / | Has ligand of interest | N | |
-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: Human cytoplasmic dynein-1 bound to one 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: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 24417 / Symmetry type: POINT | ||||||||||||||||||||||||
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