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- EMDB-41172: Cryo-EM structure of cardiac amyloid fibril from a variant ATTR I... -
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Basic information
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Title | Cryo-EM structure of cardiac amyloid fibril from a variant ATTR I84S amyloidosis patient-3, variant-type morphology | ||||||||||||
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![]() | ATTR / amyloidosis / cardiac fibril / I84S / PROTEIN FIBRIL | ||||||||||||
Function / homology | ![]() Retinoid cycle disease events / The canonical retinoid cycle in rods (twilight vision) / thyroid hormone binding / purine nucleobase metabolic process / Non-integrin membrane-ECM interactions / Retinoid metabolism and transport / hormone activity / azurophil granule lumen / Amyloid fiber formation / Neutrophil degranulation ...Retinoid cycle disease events / The canonical retinoid cycle in rods (twilight vision) / thyroid hormone binding / purine nucleobase metabolic process / Non-integrin membrane-ECM interactions / Retinoid metabolism and transport / hormone activity / azurophil granule lumen / Amyloid fiber formation / Neutrophil degranulation / extracellular space / extracellular exosome / extracellular region / identical protein binding Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
![]() | Nguyen BA / Singh V / Saelices L | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy. Authors: Binh An Nguyen / Virender Singh / Shumaila Afrin / Anna Yakubovska / Lanie Wang / Yasmin Ahmed / Rose Pedretti / Maria Del Carmen Fernandez-Ramirez / Preeti Singh / Maja Pękała / Luis O ...Authors: Binh An Nguyen / Virender Singh / Shumaila Afrin / Anna Yakubovska / Lanie Wang / Yasmin Ahmed / Rose Pedretti / Maria Del Carmen Fernandez-Ramirez / Preeti Singh / Maja Pękała / Luis O Cabrera Hernandez / Siddharth Kumar / Andrew Lemoff / Roman Gonzalez-Prieto / Michael R Sawaya / David S Eisenberg / Merrill Douglas Benson / Lorena Saelices / ![]() ![]() Abstract: ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic ...ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 38.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.9 KB 19.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 63.8 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Others | ![]() ![]() ![]() ![]() | 4.3 MB 49.3 MB 49.6 MB 49.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 752.6 KB | Display | ![]() |
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Full document | ![]() | 752.2 KB | Display | |
Data in XML | ![]() | 15.8 KB | Display | |
Data in CIF | ![]() | 21.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8tdoMC ![]() 8e7eC ![]() 8e7jC ![]() 8tdnC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | this map was used for model building | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Relion processed map
File | emd_41172_additional_1.map | ||||||||||||
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Annotation | Relion processed map | ||||||||||||
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-Additional map: reconstructed map from Relion
File | emd_41172_additional_2.map | ||||||||||||
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Annotation | reconstructed map from Relion | ||||||||||||
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Density Histograms |
-Half map: half-map 1
File | emd_41172_half_map_1.map | ||||||||||||
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Annotation | half-map 1 | ||||||||||||
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-Half map: half-map 2
File | emd_41172_half_map_2.map | ||||||||||||
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Annotation | half-map 2 | ||||||||||||
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Sample components
-Entire : Transthyretin fibrils extracted from patient heart.
Entire | Name: Transthyretin fibrils extracted from patient heart. |
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Components |
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-Supramolecule #1: Transthyretin fibrils extracted from patient heart.
Supramolecule | Name: Transthyretin fibrils extracted from patient heart. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transthyretin
Macromolecule | Name: Transthyretin / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.878902 KDa |
Sequence | String: MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIY KVEIDTKSYW KALGSSPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVVTNPKE UniProtKB: Transthyretin |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 / Details: water containing 5-10 mM EDTA |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 5.4 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |