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Open data
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Basic information
Entry | Database: PDB / ID: 5nvs | |||||||||
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Title | Human cytoplasmic dynein-1 tail in the twisted N-terminus state | |||||||||
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![]() | MOTOR PROTEIN / dynein / tail complex | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8.4 Å | |||||||||
![]() | Zhang, K. / Foster, H.E. / Carter, A.P. | |||||||||
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 | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 445.8 KB | Display | ![]() |
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PDB format | ![]() | 353 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 793.4 KB | Display | ![]() |
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Full document | ![]() | 834.6 KB | Display | |
Data in XML | ![]() | 56.7 KB | Display | |
Data in CIF | ![]() | 103.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3703MC ![]() 3698C ![]() 3704C ![]() 3705C ![]() 3706C ![]() 3707C ![]() 5nugC ![]() 5nvuC ![]() 5nw4C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Dynein heavy ... , 2 types, 2 molecules AB
#1: Protein | Mass: 79335.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Protein | Mass: 76016.109 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein , 5 types, 8 molecules DCIJKLRS
#2: Protein | Mass: 29804.609 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #8: Protein | Mass: 7251.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #9: Protein | | Mass: 8783.818 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | | Mass: 8868.924 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #13: Protein | Mass: 10230.603 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Dynein light intermediate ... , 2 types, 2 molecules FE
#4: Protein | Mass: 25379.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Protein | Mass: 25123.830 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-N-terminal dimerization ... , 2 types, 2 molecules 21
#6: Protein | Mass: 10656.127 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#7: Protein | Mass: 10571.022 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Intermediate ... , 2 types, 2 molecules MN
#11: Protein/peptide | Mass: 2315.846 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#12: Protein/peptide | Mass: 2486.056 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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 tail in the twisted N-terminus state Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 1.4 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 0.15 mg/ml / 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: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.6 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
Particle selection | Details: Particles were selected on the phase-flipped micrographs by Gautomatch. | ||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||
3D reconstruction | Resolution: 8.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 187830 / Symmetry type: POINT |