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- EMDB-3706: Human cytoplasmic dynein-1 bound to dynactin and an N-terminal co... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-3706 | |||||||||
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Title | Human cytoplasmic dynein-1 bound to dynactin and an N-terminal construct of BICD2 | |||||||||
![]() | 3D reconstruction of DDB. Motor domains has The stable portion of the dynein tail is visible, whereas the motor domains are disordered. | |||||||||
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![]() | Motor protein / dynein / dynactin / BICD | |||||||||
Function / homology | ![]() retrograde axonal transport of mitochondrion / Regulation of PLK1 Activity at G2/M Transition / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / dynactin complex / Recruitment of mitotic centrosome proteins and complexes / F-actin capping protein complex / dense body ...retrograde axonal transport of mitochondrion / Regulation of PLK1 Activity at G2/M Transition / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / dynactin complex / Recruitment of mitotic centrosome proteins and complexes / F-actin capping protein complex / dense body / barbed-end actin filament capping / Neutrophil degranulation / coronary vasculature development / dynein complex / COPI-independent Golgi-to-ER retrograde traffic / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / Recruitment of NuMA to mitotic centrosomes / aorta development / COPI-mediated anterograde transport / ventricular septum development / cortical cytoskeleton / dynein complex binding / microtubule-based process / COPI-mediated anterograde transport / axon cytoplasm / MHC class II antigen presentation / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / mitotic spindle organization / kinetochore / actin filament binding / actin binding / actin cytoskeleton organization / cell cortex / nuclear membrane / cytoskeleton / focal adhesion / centrosome / nucleoplasm / ATP binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.7 Å | |||||||||
![]() | Zhang K / Foster HE | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated. Authors: Kai Zhang / Helen E Foster / Arnaud Rondelet / Samuel E Lacey / Nadia Bahi-Buisson / Alexander W Bird / Andrew P Carter / ![]() ![]() ![]() Abstract: Cytoplasmic dynein-1 binds dynactin and cargo adaptor proteins to form a transport machine capable of long-distance processive movement along microtubules. However, it is unclear why dynein-1 moves ...Cytoplasmic dynein-1 binds dynactin and cargo adaptor proteins to form a transport machine capable of long-distance processive movement along microtubules. However, it is unclear why dynein-1 moves poorly on its own or how it is activated by dynactin. Here, we present a cryoelectron microscopy structure of the complete 1.4-megadalton human dynein-1 complex in an inhibited state known as the phi-particle. We reveal the 3D structure of the cargo binding dynein tail and show how self-dimerization of the motor domains locks them in a conformation with low microtubule affinity. Disrupting motor dimerization with structure-based mutagenesis drives dynein-1 into an open form with higher affinity for both microtubules and dynactin. We find the open form is also inhibited for movement and that dynactin relieves this by reorienting the motor domains to interact correctly with microtubules. Our model explains how dynactin binding to the dynein-1 tail directly stimulates its motor activity. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 67.4 KB 67.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.7 KB | Display | ![]() |
Images | ![]() | 124.9 KB | ||
Filedesc metadata | ![]() | 8.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 353.8 KB | Display | ![]() |
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Full document | ![]() | 353.3 KB | Display | |
Data in XML | ![]() | 12.8 KB | Display | |
Data in CIF | ![]() | 17.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5nw4MC ![]() 3698C ![]() 3703C ![]() 3704C ![]() 3705C ![]() 3707C ![]() 5nugC ![]() 5nvsC ![]() 5nvuC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | 3D reconstruction of DDB. Motor domains has The stable portion of the dynein tail is visible, whereas the motor domains are disordered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.68 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Human cytoplasmic dynein-1 bound to dynactin and an N-terminal co...
+Supramolecule #1: Human cytoplasmic dynein-1 bound to dynactin and an N-terminal co...
+Supramolecule #2: dynein-1
+Supramolecule #3: dynactin
+Supramolecule #4: BICD2
+Macromolecule #1: dynein heavy chain
+Macromolecule #2: dynein intermediate chain
+Macromolecule #3: dynein intermediate chain
+Macromolecule #4: dynein heavy chain
+Macromolecule #5: dynein N-terminal dimerization domain
+Macromolecule #6: dynein N-terminal dimerization domain
+Macromolecule #7: Robl
+Macromolecule #8: dynein light intermediate chain
+Macromolecule #9: dynein light intermediate chain
+Macromolecule #10: Arp1
+Macromolecule #11: beta-actin
+Macromolecule #12: Arp11
+Macromolecule #13: Capping protein (Actin filament) muscle Z-line, alpha 1
+Macromolecule #14: F-actin capping protein beta subunit variant II
+Macromolecule #15: dynactin shoulder complex
+Macromolecule #16: dynactin shoulder complex
+Macromolecule #17: dynactin shoulder complex
+Macromolecule #18: dynactin shoulder complex
+Macromolecule #19: Dynactin 6
+Macromolecule #20: Dynactin subunit 5
+Macromolecule #21: dynactin pointed end p62
+Macromolecule #22: p150
+Macromolecule #23: Dynactin
+Macromolecule #24: Dynactin
+Macromolecule #25: Dynactin
+Macromolecule #26: Dynactin
+Macromolecule #27: dynactin p150
+Macromolecule #28: BICD2N
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 1.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |