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Yorodumi- EMDB-12794: Cryo-EM structure of a twisted-dimer transthyretin amyloid fibril... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12794 | |||||||||
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Title | Cryo-EM structure of a twisted-dimer transthyretin amyloid fibril from vitreous body of the eye | |||||||||
Map data | ||||||||||
Sample |
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Keywords | AMYLOID FIBRIL / TRANSTHYRETIN / MISFOLDING / PROTEIN FIBRIL / ATTR AMYLOIDOSIS / V30M VARIANT / EX VIVO / VITREOUS BODY | |||||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.22 Å | |||||||||
Authors | Iakovleva I / Sauer-Eriksson AE | |||||||||
Funding support | Sweden, 1 items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structural basis for transthyretin amyloid formation in vitreous body of the eye. Authors: Irina Iakovleva / Michael Hall / Melanie Oelker / Linda Sandblad / Intissar Anan / A Elisabeth Sauer-Eriksson / Abstract: Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. ...Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_12794.map.gz | 13 MB | EMDB map data format | |
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Header (meta data) | emd-12794-v30.xml emd-12794.xml | 10.1 KB 10.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12794_fsc.xml | 7.9 KB | Display | FSC data file |
Images | emd_12794.png | 117.9 KB | ||
Filedesc metadata | emd-12794.cif.gz | 4.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12794 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12794 | HTTPS FTP |
-Validation report
Summary document | emd_12794_validation.pdf.gz | 549.7 KB | Display | EMDB validaton report |
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Full document | emd_12794_full_validation.pdf.gz | 549.2 KB | Display | |
Data in XML | emd_12794_validation.xml.gz | 10.4 KB | Display | |
Data in CIF | emd_12794_validation.cif.gz | 13.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12794 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12794 | HTTPS FTP |
-Related structure data
Related structure data | 7ob4MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_12794.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.041 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Transthyretin derived amyloid fibril (V30M) from vitreous body
Entire | Name: Transthyretin derived amyloid fibril (V30M) from vitreous body |
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Components |
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-Supramolecule #1: Transthyretin derived amyloid fibril (V30M) from vitreous body
Supramolecule | Name: Transthyretin derived amyloid fibril (V30M) from vitreous body type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Vitreous body of the eye |
-Macromolecule #1: Transthyretin
Macromolecule | Name: Transthyretin / type: protein_or_peptide / ID: 1 / Number of copies: 14 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.809426 KDa |
Sequence | String: GPTGTGESKC PLMVKVLDAV RGSPAINVAM HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVVTNPKE UniProtKB: Transthyretin |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | helical array |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 28.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |