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- EMDB-49578: Cryo-EM structure of amyloid fibril extracted from the heart of a... -

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Basic information

Entry
Database: EMDB / ID: EMD-49578
TitleCryo-EM structure of amyloid fibril extracted from the heart of a variant ATTR D38A amyloidosis patient
Map dataauto-sharpened map of post-processed map. It was used for model building
Sample
  • Complex: Amyloid fibrils of transthyretin
    • Protein or peptide: Transthyretin
KeywordsTransthyretin / Amyloidosis / Systemic amyloidosis / ATTR / Cardiac / 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) / purine nucleobase metabolic process / hormone binding / 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) / purine nucleobase metabolic process / hormone binding / 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: 3.6 Å
AuthorsNguyen B / Afrin S / Saelices L
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)1DP2HL163810-01 United States
American Heart Association847236 United States
CitationJournal: To Be Published
Title: Cardiac amyloid fibrils extracted from a ATTRv-D38A amyloidosis patient
Authors: Nguyen BA / Saelices L
History
DepositionMar 5, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateFeb 11, 2026-
Current statusFeb 11, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_49578.png

Downloads & links

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Map

FileDownload / File: emd_49578.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationauto-sharpened map of post-processed map. It was used for model building
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.82 Å/pix.
x 300 pix.
= 246. Å		0.82 Å/pix.
x 300 pix.
= 246. Å		0.82 Å/pix.
x 300 pix.
= 246. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.82 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 8.25
Minimum - Maximum-21.317682000000001 - 31.442589000000002
Average (Standard dev.)0.000000000004153 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 246.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_49578_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: combined map from two half-maps

Fileemd_49578_additional_1.map
Annotationcombined map from two half-maps
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Post-processed map

Fileemd_49578_additional_2.map
AnnotationPost-processed map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half-map1

Fileemd_49578_half_map_1.map
Annotationhalf-map1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half-map2

Fileemd_49578_half_map_2.map
Annotationhalf-map2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Amyloid fibrils of transthyretin

EntireName: Amyloid fibrils of transthyretin
Components
  • Complex: Amyloid fibrils of transthyretin
    • Protein or peptide: Transthyretin

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Supramolecule #1: Amyloid fibrils of transthyretin

SupramoleculeName: Amyloid fibrils of transthyretin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Transthyretin amyloid extracted from cardiac tissue of ATTv-D38A amyloidosis patient
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: Heart
Molecular weightTheoretical: 13.77736 KDa
SequenceString:
GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVVTNPKE

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 eluted in ice-cold 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
Detailsextracted from cardiac tissue of a ATTRv-D38A amyloidosis patient

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 4467 / Average exposure time: 4.0 sec. / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 1.5 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: 4.74 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.25 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 36014
CTF correctionSoftware - Name: RELION (ver. 4.0) / Type: NONE
Segment selectionNumber selected: 46577 / Software - Name: RELION (ver. 4.0)
Startup modelType of model: INSILICO MODEL
In silico model: model was generated by relion_helix_inimodel2d script.
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

8e7d


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

PDB-9nnn:
Cryo-EM structure of amyloid fibril extracted from the heart of a variant ATTR D38A amyloidosis patient

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