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- EMDB-44462: Cryo-EM structure of cardiac amyloid fibril from a variant ATTRV1... -

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Basic information

Entry
Database: EMDB / ID: EMD-44462
TitleCryo-EM structure of cardiac amyloid fibril from a variant ATTRV122delta, single filament morphology
Map dataprimary map for model building
Sample
  • Complex: fibril of ATTRV122delta
    • Protein or peptide: Transthyretin
KeywordsATTR / Systemic amyloidosis / V122delta / amyloid / PROTEIN FIBRIL
Function / homology
Function and homology information


Defective visual phototransduction due to STRA6 loss of function / negative regulation of glomerular filtration / The canonical retinoid cycle in rods (twilight vision) / hormone binding / purine nucleobase metabolic process / Non-integrin membrane-ECM interactions / molecular sequestering activity / phototransduction, visible light / retinoid metabolic process / Retinoid metabolism and transport ...Defective visual phototransduction due to STRA6 loss of function / negative regulation of glomerular filtration / The canonical retinoid cycle in rods (twilight vision) / hormone binding / purine nucleobase metabolic process / Non-integrin membrane-ECM interactions / molecular sequestering activity / phototransduction, visible light / retinoid metabolic process / Retinoid metabolism and transport / hormone activity / azurophil granule lumen / Amyloid fiber formation / Neutrophil degranulation / protein-containing complex binding / protein-containing complex / extracellular space / extracellular exosome / extracellular region / identical protein binding
Similarity search - Function
Transthyretin, conserved site / Transthyretin signature 2. / Transthyretin, thyroxine binding site / Transthyretin signature 1. / Transthyretin / Transthyretin/hydroxyisourate hydrolase / Transthyretin/hydroxyisourate hydrolase domain / Transthyretin/hydroxyisourate hydrolase domain superfamily / HIUase/Transthyretin family
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 3.63 Å
AuthorsNguyen BA / Ahmed Y / Saelices L
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)DP2-HL163810 United States
American Heart Association847236 United States
Welch FoundationI-2121-20220331 United States
CitationJournal: To Be Published
Title: Cryo-EM structure of cardiac amyloid fibril from a variant ATTRV122delta, single filament morphology
Authors: Nguyen BA / Ahmed Y / Saelices L
History
DepositionApr 12, 2024-
Header (metadata) releaseOct 15, 2025-
Map releaseOct 15, 2025-
UpdateOct 15, 2025-
Current statusOct 15, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_44462.png

Downloads & links

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Map

FileDownload / File: emd_44462.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationprimary map for model building
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 192 pix.
= 181.632 Å		0.95 Å/pix.
x 192 pix.
= 181.632 Å		0.95 Å/pix.
x 192 pix.
= 181.632 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.946 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0355
Minimum - Maximum-0.11273546 - 0.16834618
Average (Standard dev.)0.00041120476 (±0.006674432)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 181.63199 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_44462_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: map after 3D refine

Fileemd_44462_additional_1.map
Annotationmap after 3D refine
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: halfmap 01

Fileemd_44462_half_map_1.map
Annotationhalfmap 01
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: halfmap 02

Fileemd_44462_half_map_2.map
Annotationhalfmap 02
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : fibril of ATTRV122delta

EntireName: fibril of ATTRV122delta
Components
  • Complex: fibril of ATTRV122delta
    • Protein or peptide: Transthyretin

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Supramolecule #1: fibril of ATTRV122delta

SupramoleculeName: fibril of ATTRV122delta / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: fibril extracted from cardiac tissue, postmortem.
Source (natural)Organism: Homo sapiens (human) / Organ: Heart / Tissue: Cardiac

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Macromolecule #1: Transthyretin

MacromoleculeName: Transthyretin / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human) / Organ: Heart / Tissue: Cardiac
Molecular weightTheoretical: 13.678229 KDa
SequenceString:
GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVTNPKE

UniProtKB: Transthyretin

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 7 / Component - Formula: H2O / Component - Name: water / Details: ice-chilled water
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV
Detailsfibrils were extracted from cardiac tissue using a water-based extraction method.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 5759 / Average exposure time: 3.67 sec. / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

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Image processing

Final reconstructionNumber classes used: 1
Applied symmetry - Helical parameters - Δz: 4.9 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.27 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.1) / Number images used: 32315
CTF correctionSoftware - Name: CTFFIND (ver. 4.1) / Type: NONE
Segment selectionNumber selected: 498426 / Software - Name: RELION (ver. 4.0)
Startup modelType of model: INSILICO MODEL / In silico model: featureless cylinder
Final angle assignmentType: NOT APPLICABLE / Software - Name: RELION (ver. 4.1)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

8tdn


Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT / Overall B value: 117
Output model

PDB-9bdm:
Cryo-EM structure of cardiac amyloid fibril from a variant ATTRV122delta, single filament morphology

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