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Open data
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Basic information
Entry | Database: PDB / ID: 8dyv | |||||||||
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Title | Structure of human cytoplasmic dynein-1 bound to one Lis1 | |||||||||
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![]() | MOTOR PROTEIN / dynein / transport | |||||||||
Function / homology | ![]() 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 / microtubule organizing center organization / platelet activating factor metabolic process ...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 / microtubule organizing center organization / platelet activating factor metabolic process / acrosome assembly / radial glia-guided pyramidal neuron migration / cerebral cortex neuron differentiation / positive regulation of intracellular transport / 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 / 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 / microtubule associated complex / kinesin complex / dynein intermediate chain binding / cochlea development / dynein complex binding / 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 / 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 / kinetochore / cerebral cortex development / 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 | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.97 Å | |||||||||
![]() | Reimer, J.M. / DeSantis, M. / Reck-Peterson, S.L. / Leschziner, A.E. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1 MB | Display | ![]() |
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PDB format | ![]() | 878 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27783MC ![]() 8dyuC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() | ||||
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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.) ![]() ![]() ![]() | ||||
#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 |
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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: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
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) |
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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 | ||||||||||||||||||||||||
Refine LS restraints |
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