[English] 日本語
Yorodumi
- EMDB-41172: Cryo-EM structure of cardiac amyloid fibril from a variant ATTR I... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-41172
TitleCryo-EM structure of cardiac amyloid fibril from a variant ATTR I84S amyloidosis patient-3, variant-type morphology
Map datathis map was used for model building
Sample
  • Complex: Transthyretin fibrils extracted from patient heart.
    • Protein or peptide: Transthyretin
KeywordsATTR / amyloidosis / cardiac fibril / I84S / PROTEIN FIBRIL
Function / homology
Function and homology information


Retinoid cycle disease events / thyroid hormone binding / The canonical retinoid cycle in rods (twilight vision) / Non-integrin membrane-ECM interactions / purine nucleobase metabolic process / Retinoid metabolism and transport / hormone activity / azurophil granule lumen / Amyloid fiber formation / Neutrophil degranulation ...Retinoid cycle disease events / thyroid hormone binding / The canonical retinoid cycle in rods (twilight vision) / Non-integrin membrane-ECM interactions / purine nucleobase metabolic process / 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
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: 3.1 Å
AuthorsNguyen BA / Singh V / 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 AssociationCareer Development Award 847236 United States
Welch FoundationResearch Award I-2121-20220331 United States
CitationJournal: Nat Commun / Year: 2024
Title: Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.
Authors: Binh An Nguyen / Virender Singh / Shumaila Afrin / Anna Yakubovska / Lanie Wang / Yasmin Ahmed / Rose Pedretti / Maria Del Carmen Fernandez-Ramirez / Preeti Singh / Maja Pękała / Luis O ...Authors: Binh An Nguyen / Virender Singh / Shumaila Afrin / Anna Yakubovska / Lanie Wang / Yasmin Ahmed / Rose Pedretti / Maria Del Carmen Fernandez-Ramirez / Preeti Singh / Maja Pękała / Luis O Cabrera Hernandez / Siddharth Kumar / Andrew Lemoff / Roman Gonzalez-Prieto / Michael R Sawaya / David S Eisenberg / Merrill Douglas Benson / Lorena Saelices /
Abstract: ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic ...ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.
History
DepositionJul 4, 2023-
Header (metadata) releaseDec 13, 2023-
Map releaseDec 13, 2023-
UpdateMar 13, 2024-
Current statusMar 13, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_41172.png

Downloads & links

-
Map

FileDownload / File: emd_41172.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationthis map was used for model building
Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 10.5
Minimum - Maximum-29.106482 - 45.759524999999996
Average (Standard dev.)-0.000000000002638 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 212.48 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: Relion processed map

Fileemd_41172_additional_1.map
AnnotationRelion processed map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: reconstructed map from Relion

Fileemd_41172_additional_2.map
Annotationreconstructed map from Relion
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half-map 1

Fileemd_41172_half_map_1.map
Annotationhalf-map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half-map 2

Fileemd_41172_half_map_2.map
Annotationhalf-map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Transthyretin fibrils extracted from patient heart.

EntireName: Transthyretin fibrils extracted from patient heart.
Components
  • Complex: Transthyretin fibrils extracted from patient heart.
    • Protein or peptide: Transthyretin

-
Supramolecule #1: Transthyretin fibrils extracted from patient heart.

SupramoleculeName: Transthyretin fibrils extracted from patient heart. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Transthyretin

MacromoleculeName: Transthyretin / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15.878902 KDa
SequenceString:
MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIY KVEIDTKSYW KALGSSPFHE HAEVVFTAND SGPRRYTIAA LLSPYSYSTT AVVTNPKE

UniProtKB: Transthyretin

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

BufferpH: 7.4 / Details: water containing 5-10 mM EDTA
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.9 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average exposure time: 5.4 sec. / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: INSILICO MODEL / In silico model: Featureless cylinder
Final angle assignmentType: NOT APPLICABLE
Final reconstructionApplied symmetry - Helical parameters - Δz: 4.8 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.42 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Details: resolution was estimated using RELION 4 / Number images used: 51411
FSC plot (resolution estimation)

+
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