[English] 日本語
Yorodumi
- EMDB-46487: Cryo-EM structure of amyloid fibril extracted from kidney of a va... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-46487
TitleCryo-EM structure of amyloid fibril extracted from kidney of a variant ATTR T60A amyloidosis patient 3
Map dataused for model-building
Sample
  • Tissue: Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient
    • Protein or peptide: Transthyretin
KeywordsTransthyretin / Amyloidosis / ATTR / Kidney / 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: 3.19 Å
AuthorsNguyen AB / Fernandez-Ramirez MC / 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: Structure / Year: 2025
Title: Structural and molecular homogeneity of ATTRv-T60A amyloid fibrils across patients and organs.
Authors: Maria Del Carmen Fernandez-Ramirez / Binh A Nguyen / Shumaila Afrin / Virender Singh / Bret Evers / John M Shelton / Christian Lopez Escobar / Parker Bassett / Lanie Wang / Maja Pękała / ...Authors: Maria Del Carmen Fernandez-Ramirez / Binh A Nguyen / Shumaila Afrin / Virender Singh / Bret Evers / John M Shelton / Christian Lopez Escobar / Parker Bassett / Lanie Wang / Maja Pękała / Yasmin Ahmed / Luis O Cabrera Hernandez / Rose Pedretti / Preeti Singh / Jacob Canepa / Aleksandra Wosztyl / Yang Li / David R Boyer / Qin Cao / Lorena Saelices /
Abstract: Transthyretin amyloidosis is a systemic protein misfolding disorder with diverse clinical phenotypes, including cardiomyopathy, polyneuropathy, or a combination of both. While structural polymorphism ...Transthyretin amyloidosis is a systemic protein misfolding disorder with diverse clinical phenotypes, including cardiomyopathy, polyneuropathy, or a combination of both. While structural polymorphism of amyloid fibrils has been linked to disease heterogeneity in neurodegenerative disorders, its role in transthyretin amyloidosis remains unclear. Here, we used cryo-electron microscopy to analyze ex vivo fibrils extracted from the hearts of three patients carrying the T60A mutation, a variant associated with mixed cardiac and neuropathic symptoms. In one patient, we additionally examined fibrils from the thyroid, kidney, and liver. All fibrils across patients and tissues adopted a single morphology previously associated with cardiomyopathy. Complementary molecular analyses revealed high compositional homogeneity. Notably, we extracted fibrils from the liver, an organ considered fibril-free, with seeding capacity in vitro. These findings suggest structural homogeneity as a hallmark of cardiac and mixed phenotypes, and provide a mechanistic rationale for the transmission of amyloidosis following domino liver transplantation.
History
DepositionAug 8, 2024-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateOct 29, 2025-
Current statusOct 29, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_46487.png

Downloads & links

-
Map

FileDownload / File: emd_46487.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationused for model-building
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.95 Å/pix.
x 256 pix.
= 242.176 Å		0.95 Å/pix.
x 256 pix.
= 242.176 Å		0.95 Å/pix.
x 256 pix.
= 242.176 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: 7.8
Minimum - Maximum-30.889527999999999 - 47.819412
Average (Standard dev.)-0.000000000004546 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 242.176 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_46487_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: combined map from two half-maps

Fileemd_46487_additional_1.map
Annotationcombined map from two half-maps
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half-map 01

Fileemd_46487_half_map_1.map
Annotationhalf-map 01
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half-map 02

Fileemd_46487_half_map_2.map
Annotationhalf-map 02
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient

EntireName: Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient
Components
  • Tissue: Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient
    • Protein or peptide: Transthyretin

-
Supramolecule #1: Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient

SupramoleculeName: Amyloid fibril from kidney of a variant ATTR T60A amyloidosis patient
type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney

-
Macromolecule #1: Transthyretin

MacromoleculeName: Transthyretin / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney
Molecular weightTheoretical: 13.747334 KDa
SequenceString:
GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS ESGELHGLTA EEEFVEGIYK VEIDTKSYWK ALGISPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVVTNPKE

UniProtKB: Transthyretin

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statehelical array

-
Sample preparation

BufferpH: 7
Details: We used water as the buffer for the final elution of fibrils
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.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 6699 / Average exposure time: 5.29 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 / Cs: 2.7 mm / Nominal defocus max: 2.1 µm / Nominal defocus min: 0.9 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Final reconstructionNumber classes used: 2
Applied symmetry - Helical parameters - Δz: 4.91 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.17 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 57895
CTF correctionSoftware - Name: RELION (ver. 4.0) / Software - details: CTFFIND-4.1 / Type: NONE
Segment selectionNumber selected: 1271167 / Software - Name: Topaz / Details: particle boxsize of 256 px
Startup modelType of model: OTHER / Details: Featureless cylinder
Final angle assignmentType: NOT APPLICABLE / Software - Name: RELION (ver. 4.0)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

9d24


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

PDB-9d27:
Cryo-EM structure of amyloid fibril extracted from kidney of a variant ATTR T60A amyloidosis patient 3

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more