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Yorodumi- PDB-6hud: Cryo-EM structure of cardiac amyloid fibrils from an immunoglobul... -
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-Basic information
Entry | Database: PDB / ID: 6hud | |||||||||||||||
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Title | Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain (AL) amyloidosis patient. | |||||||||||||||
Components | Monoclonal immunoglobulin light chains (LC) | |||||||||||||||
Keywords | PROTEIN FIBRIL / immunoglobulin light chains / amyloid cardiomyopathy / ex-vivo cryo-EM / helical reconstruction | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4 Å | |||||||||||||||
Authors | Paissoni, C. / Camilloni, C. | |||||||||||||||
Funding support | Italy, 4items
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Citation | Journal: Nat Commun / Year: 2019 Title: Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient. Authors: Paolo Swuec / Francesca Lavatelli / Masayoshi Tasaki / Cristina Paissoni / Paola Rognoni / Martina Maritan / Francesca Brambilla / Paolo Milani / Pierluigi Mauri / Carlo Camilloni / Giovanni ...Authors: Paolo Swuec / Francesca Lavatelli / Masayoshi Tasaki / Cristina Paissoni / Paola Rognoni / Martina Maritan / Francesca Brambilla / Paolo Milani / Pierluigi Mauri / Carlo Camilloni / Giovanni Palladini / Giampaolo Merlini / Stefano Ricagno / Martino Bolognesi / Abstract: Systemic light chain amyloidosis (AL) is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart ...Systemic light chain amyloidosis (AL) is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.0 Å resolution cryo-electron microscopy map and molecular model of amyloid fibrils extracted from the heart of an AL amyloidosis patient with severe amyloid cardiomyopathy. The helical fibrils are composed of a single protofilament, showing typical 4.9 Å stacking and cross-β architecture. Two distinct polypeptide stretches (total of 77 residues) from the LC variable domain (V) fit the fibril density. Despite V high sequence variability, residues stabilizing the fibril core are conserved through different cardiotoxic V, highlighting structural motifs that may be common to misfolding-prone LCs. Our data shed light on the architecture of LC amyloids, correlate amino acid sequences with fibril assembly, providing the grounds for development of innovative medicines. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6hud.cif.gz | 72.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hud.ent.gz | 57.4 KB | Display | PDB format |
PDBx/mmJSON format | 6hud.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6hud_validation.pdf.gz | 638.7 KB | Display | wwPDB validaton report |
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Full document | 6hud_full_validation.pdf.gz | 639.1 KB | Display | |
Data in XML | 6hud_validation.xml.gz | 22 KB | Display | |
Data in CIF | 6hud_validation.cif.gz | 31.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hu/6hud ftp://data.pdbj.org/pub/pdb/validation_reports/hu/6hud | HTTPS FTP |
-Related structure data
Related structure data | 0274MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Antibody | Mass: 14620.864 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: Heart |
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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 |
-Sample preparation
Component | Name: Cardiac amyloid fibril from an immunoglobulin light chain (AL) amyloidosis patient Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) / Tissue: Heart |
Buffer solution | pH: 7 |
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: 278 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 120000 X / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: OTHER |
Image recording | Average exposure time: 1 sec. / Electron dose: 50 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of real images: 1680 |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -1.608 ° / Axial rise/subunit: 4.903 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 104689 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 21031 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |