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- EMDB-44466: Cryo-EM structure of cardiac amyloid fibril from a variant ATTRV1... -

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Basic information

Entry
Database: EMDB / ID: EMD-44466
TitleCryo-EM structure of cardiac amyloid fibril from a variant ATTRV122delta, double filament morphology 1
Map dataPrimary map for model building
Sample
  • Complex: Transthyretin fibrils
    • Protein or peptide: Transthyretin
KeywordsATTR / transthyretin amyloidosis / V122delta / ex vivo / 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 / molecular sequestering activity / Non-integrin membrane-ECM interactions / 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 / molecular sequestering activity / Non-integrin membrane-ECM interactions / 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: 3.82 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, double filament morphology 1
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_44466.png

Downloads & links

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Map

FileDownload / File: emd_44466.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPrimary map for model building
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.95 Å/pix.
x 320 pix.
= 302.72 Å		0.95 Å/pix.
x 320 pix.
= 302.72 Å		0.95 Å/pix.
x 320 pix.
= 302.72 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: 4.38
Minimum - Maximum-18.366776000000002 - 27.798206
Average (Standard dev.)0.000000000003617 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 302.72 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_44466_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: reconstructed map from 3Drefine

Fileemd_44466_additional_1.map
Annotationreconstructed map from 3Drefine
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: halfmap 01

Fileemd_44466_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_44466_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 : Transthyretin fibrils

EntireName: Transthyretin fibrils
Components
  • Complex: Transthyretin fibrils
    • Protein or peptide: Transthyretin

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Supramolecule #1: Transthyretin fibrils

SupramoleculeName: Transthyretin fibrils / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
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: 10 / 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 / Details: Fibrils were purified in 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

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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: 4.88 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.15 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.82 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 40635
CTF correctionSoftware - Name: CTFFIND (ver. 4.1) / Type: NONE
Segment selectionNumber selected: 726223 / Software - Name: RELION (ver. 4.0)
Startup modelType of model: INSILICO MODEL
In silico model: generated from 2D class average images by RELION
Final angle assignmentType: NOT APPLICABLE / Software - Name: RELION (ver. 4.0)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

9bdm


Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT / Overall B value: 97
Output model

PDB-9bdr:
Cryo-EM structure of cardiac amyloid fibril from a variant ATTRV122delta, double filament morphology 1

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