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Yorodumi- EMDB-50272: Additional cryo-EM structure of cardiac amyloid AL59 - mixed polymorph -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-50272 | |||||||||
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Title | Additional cryo-EM structure of cardiac amyloid AL59 - mixed polymorph | |||||||||
Map data | ||||||||||
Sample |
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Keywords | systemic AL amyloid fibril / PROTEIN FIBRIL | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Schulte T / Speranzini V / Chaves-Sanjuan A / Milazzo M / Ricagno S | |||||||||
Funding support | Italy, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis. Authors: Tim Schulte / Antonio Chaves-Sanjuan / Valentina Speranzini / Kevin Sicking / Melissa Milazzo / Giulia Mazzini / Paola Rognoni / Serena Caminito / Paolo Milani / Chiara Marabelli / ...Authors: Tim Schulte / Antonio Chaves-Sanjuan / Valentina Speranzini / Kevin Sicking / Melissa Milazzo / Giulia Mazzini / Paola Rognoni / Serena Caminito / Paolo Milani / Chiara Marabelli / Alessandro Corbelli / Luisa Diomede / Fabio Fiordaliso / Luigi Anastasia / Carlo Pappone / Giampaolo Merlini / Martino Bolognesi / Mario Nuvolone / Rubén Fernández-Busnadiego / Giovanni Palladini / Stefano Ricagno / Abstract: Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC ...Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_50272.map.gz | 8.2 MB | EMDB map data format | |
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Header (meta data) | emd-50272-v30.xml emd-50272.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_50272_fsc.xml | 12.1 KB | Display | FSC data file |
Images | emd_50272.png | 82 KB | ||
Masks | emd_50272_msk_1.map | 149.9 MB | Mask map | |
Filedesc metadata | emd-50272.cif.gz | 5.4 KB | ||
Others | emd_50272_half_map_1.map.gz emd_50272_half_map_2.map.gz | 118.3 MB 118.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-50272 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-50272 | HTTPS FTP |
-Validation report
Summary document | emd_50272_validation.pdf.gz | 809.1 KB | Display | EMDB validaton report |
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Full document | emd_50272_full_validation.pdf.gz | 808.6 KB | Display | |
Data in XML | emd_50272_validation.xml.gz | 19.4 KB | Display | |
Data in CIF | emd_50272_validation.cif.gz | 25.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50272 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50272 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_50272.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.889 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_50272_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_50272_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_50272_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Monoclonal immunoglobulin light chains (LC), fibrillar form
Entire | Name: Monoclonal immunoglobulin light chains (LC), fibrillar form |
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Components |
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-Supramolecule #1: Monoclonal immunoglobulin light chains (LC), fibrillar form
Supramolecule | Name: Monoclonal immunoglobulin light chains (LC), fibrillar form type: tissue / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Amyloid fibrils extracted ex vivo from cardiac tissue of AL patient |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Monoclonal immunoglobulin light chains (LC)
Macromolecule | Name: Monoclonal immunoglobulin light chains (LC) / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.923335 KDa |
Sequence | String: SFELTQPSSV SVSPGQTANI TCSGGYLGET YRSWYQQKPG QSPVLVIYQS SKRPSGIPGR FSGSNSGNTA TLTISGTQPL DEADYFCQA WDFTSVVFGG GTKLTVLGQP KAAPSVTLFP PSSEELQANK ATL |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number real images: 2049 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 120000 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |