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Open data
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Basic information
Entry | Database: PDB / ID: 9cww | |||||||||||||||||||||||||||
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Title | Structure of D10-NT amyloid fibrils | |||||||||||||||||||||||||||
![]() | Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial | |||||||||||||||||||||||||||
![]() | PROTEIN FIBRIL / CHCHD10 / Amyloid Fibril | |||||||||||||||||||||||||||
Function / homology | ![]() : / MICOS complex / mitochondria-nucleus signaling pathway / positive regulation of cristae formation / positive regulation of mitochondrial transcription / stabilization of membrane potential / maintenance of synapse structure / Mitochondrial protein import / maintenance of protein location in nucleus / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway ...: / MICOS complex / mitochondria-nucleus signaling pathway / positive regulation of cristae formation / positive regulation of mitochondrial transcription / stabilization of membrane potential / maintenance of synapse structure / Mitochondrial protein import / maintenance of protein location in nucleus / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / oxidative phosphorylation / mitochondrion organization / mitochondrial intermembrane space / protein-containing complex assembly / mitochondrion / nucleus Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||||||||||||||||||||
![]() | Lv, G. / Eliezer, D. | |||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration. Authors: Guohua Lv / Nicole M Sayles / Yun Huang / Chiara Mancinelli / Kevin McAvoy / Neil A Shneider / Giovanni Manfredi / Hibiki Kawamata / David Eliezer / ![]() Abstract: Mitochondrial proteins CHCHD10 and CHCHD2 are mutated in rare cases of heritable FTD, ALS and PD and aggregate in tissues affected by these diseases. Here, we show that both proteins form amyloid ...Mitochondrial proteins CHCHD10 and CHCHD2 are mutated in rare cases of heritable FTD, ALS and PD and aggregate in tissues affected by these diseases. Here, we show that both proteins form amyloid fibrils and report cryo-EM structures of fibrils formed from their disordered N-terminal domains. The ordered cores of these fibrils are comprised of a region highly conserved between the two proteins, and a subset of the CHCHD10 and CHCHD2 fibril structures share structural similarities and appear compatible with sequence variations in this region. In contrast, disease-associated mutations p.S59L in CHCHD10 and p.T61I in CHCHD2, situated within the ordered cores of these fibrils, cannot be accommodated by the wildtype structures and promote different protofilament folds and fibril structures. These results link CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration and further suggest that fibril formation by the WT proteins could also be involved in disease etiology. | |||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 50.3 KB | Display | ![]() |
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PDB format | ![]() | 29.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 954.2 KB | Display | ![]() |
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Full document | ![]() | 954.8 KB | Display | |
Data in XML | ![]() | 21.6 KB | Display | |
Data in CIF | ![]() | 30.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 45976MC ![]() 9oyoC ![]() 9oyqC ![]() 9oyrC ![]() 9oysC ![]() 9oytC ![]() 9oywC 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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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: PRO / Beg label comp-ID: PRO / End auth comp-ID: GLY / End label comp-ID: GLY / Auth seq-ID: 42 - 75 / Label seq-ID: 42 - 75
NCS oper:
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Components
#1: Protein | Mass: 9252.316 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Has protein modification | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: CHCHD10 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293.15 K |
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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 / Nominal magnification: 64000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 900 nm / Cs: 0.01 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 51.82 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 178.845 ° / Axial rise/subunit: 2.365 Å / Axial symmetry: C21 | ||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 667405 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 33.04 Å2 | ||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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Refine LS restraints NCS |
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