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- PDB-6yej: Cryo-EM structure of the Full-length disease type human Huntingtin -
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Open data
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Basic information
Entry | Database: PDB / ID: 6yej | |||||||||
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Title | Cryo-EM structure of the Full-length disease type human Huntingtin | |||||||||
![]() | Huntingtin | |||||||||
![]() | STRUCTURAL PROTEIN / multivalent scaffold platform / PROTEIN BINDING | |||||||||
Function / homology | ![]() regulation of cAMP-dependent protein kinase activity / : / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / positive regulation of mitophagy / profilin binding / vesicle transport along microtubule / positive regulation of cilium assembly ...regulation of cAMP-dependent protein kinase activity / : / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / positive regulation of mitophagy / profilin binding / vesicle transport along microtubule / positive regulation of cilium assembly / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / presynaptic cytosol / positive regulation of aggrephagy / positive regulation of lipophagy / dynein intermediate chain binding / postsynaptic cytosol / beta-tubulin binding / Golgi organization / establishment of mitotic spindle orientation / dynactin binding / Regulation of MECP2 expression and activity / autophagosome / inclusion body / heat shock protein binding / centriole / negative regulation of extrinsic apoptotic signaling pathway / protein destabilization / cytoplasmic vesicle membrane / kinase binding / p53 binding / late endosome / transmembrane transporter binding / early endosome / positive regulation of apoptotic process / axon / dendrite / apoptotic process / perinuclear region of cytoplasm / Golgi apparatus / endoplasmic reticulum / protein-containing complex / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 18.2 Å | |||||||||
![]() | Tame, G. / Jung, T. / Dal Perraro, M. / Hebert, H. / Song, J. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain. Authors: Taeyang Jung / Baehyun Shin / Giorgio Tamo / Hyeongju Kim / Ravi Vijayvargia / Alexander Leitner / Maria J Marcaida / Juan Astorga-Wells / Roy Jung / Ruedi Aebersold / Matteo Dal Peraro / ...Authors: Taeyang Jung / Baehyun Shin / Giorgio Tamo / Hyeongju Kim / Ravi Vijayvargia / Alexander Leitner / Maria J Marcaida / Juan Astorga-Wells / Roy Jung / Ruedi Aebersold / Matteo Dal Peraro / Hans Hebert / Ihn Sik Seong / Ji-Joon Song / ![]() ![]() ![]() ![]() Abstract: The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural ...The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural information on its HEAT-repeat domains. Here, we present analyses of the impact of polyQ length on the structure and function of HTT via an integrative structural and biochemical approach. The cryo-EM analysis of normal (Q23) and disease (Q78) type HTTs shows that the structures of apo HTTs significantly differ from the structure of HTT in a HAP40 complex and that the polyQ expansion induces global structural changes in the relative movements among the HTT domains. In addition, we show that the polyQ expansion alters the phosphorylation pattern across HTT and that Ser2116 phosphorylation in turn affects the global structure and function of HTT. These results provide a molecular basis for the effect of the polyQ segment on HTT structure and activity, which may be important for HTT pathology. | |||||||||
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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PDBx/mmCIF format | ![]() | 374.6 KB | Display | ![]() |
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PDB format | ![]() | 287.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 10793MC ![]() 4937C ![]() 4944C ![]() 6rmhC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 355278.719 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-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: Full-length human disease-type huntingtin / Type: ORGANELLE OR CELLULAR COMPONENT Details: A disease type huntingtin with 78 polyglutamine repeat tract Entity ID: all / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.35 MDa / Experimental value: YES | |||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.08 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: HTT was mixed with final 0.05% of Octyl glucoside. | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 288 K / Details: 30 seconds incubation 8 seconds blotting |
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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 / Calibrated magnification: 47170 X / Nominal defocus max: 400 nm / Nominal defocus min: 400 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 6 sec. / Electron dose: 33.6 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 1500 |
EM imaging optics | Energyfilter slit width: 20 eV / Phase plate: VOLTA PHASE PLATE |
Image scans | Movie frames/image: 24 / Used frames/image: 1-24 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 45039 / Details: manual picking | |||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 18.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 21781 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6EZ8 Pdb chain-ID: A / Pdb chain residue range: 91-3198 |