[English] 日本語
Yorodumi
- EMDB-50442: Cryo-EM Structure of Amyloid-beta Fibrils from Individual Carryin... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-50442
TitleCryo-EM Structure of Amyloid-beta Fibrils from Individual Carrying the Uppsala AbetaUpp(1-42)delta(19-24) mutation
Map dataprimary map
Sample
  • Tissue: amyloid-beta fibrils
    • Protein or peptide: amyloid-beta
KeywordsAmyloid Fibril / PROTEIN FIBRIL
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 5.9 Å
AuthorsZielinski M / Peralta Reyes FS / Gremer L / Pagnon de la Vega M / Roeder C / Heidler TV / Syvaenen S / Willbold D / Sehlin D / Ingelsson M / Schroeder GF
Funding support Germany, 1 items
OrganizationGrant numberCountry
Helmholtz AssociationIVF Germany
CitationJournal: Acta Neuropathol Commun / Year: 2025
Title: Cryo-EM studies of amyloid-β fibrils from human and murine brains carrying the Uppsala APP mutation (Δ690-695).
Authors: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Simon Sommerhage / María Pagnon de la Vega / Christine Röder / Thomas V Heidler / Stina Syvänen / Dieter Willbold / Dag Sehlin ...Authors: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Simon Sommerhage / María Pagnon de la Vega / Christine Röder / Thomas V Heidler / Stina Syvänen / Dieter Willbold / Dag Sehlin / Martin Ingelsson / Gunnar F Schröder /
Abstract: Today, 13 intra-amyloid-β (Aβ) amyloid precursor protein (APP) gene mutations are known to cause familial Alzheimer's disease (AD). Most of them are point mutations causing an increased production ...Today, 13 intra-amyloid-β (Aβ) amyloid precursor protein (APP) gene mutations are known to cause familial Alzheimer's disease (AD). Most of them are point mutations causing an increased production or a change in the conformation of Aβ. The Uppsala APP mutation (Δ690-695 in APP, Δ19-24 in Aβ) is the first known multi-codon deletion causing autosomal dominant AD. Here, we applied cryo-electron microscopy (cryo-EM) to investigate the structure of Aβ fibrils with the Uppsala APP mutation from tg-UppSwe mouse brain tissue. Murine AβUpp(1-42) are made of two identical S-shaped protofilaments with an ordered fibril core of S8-A42. The murine Aβ fold is almost identical to previously described human type II filaments, although the amino acid sequences differ considerably. In addition, we report the cryo-EM structure of Aβ fibrils from the temporal cortex of a patient with the Uppsala APP mutation. The observed structure of the human Aβ fold closely resembles previously described type I fibrils. Structural modeling suggests that these fibrils are composed of wild-type Aβ, which implies that AβUpp may be less soluble and thus not readily accessible for cryo-EM image processing and structure determination. Additionally, from the human sample we determined the structures of tau paired helical filaments and tau straight filaments, which are identical to those found in sporadic AD cases. Finally, we present the 3D cryo-EM structures of four dominant AβUpp(1-42) fibril polymorphs, formed in vitro. All four polymorphs differ from the observed folds of Uppsala Aβ in murine and human brain tissue, respectively.
History
DepositionMay 26, 2024-
Header (metadata) releaseJun 11, 2025-
Map releaseJun 11, 2025-
UpdateOct 22, 2025-
Current statusOct 22, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_50442.png

Downloads & links

-
Map

FileDownload / File: emd_50442.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationprimary map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.81 Å/pix.
x 300 pix.
= 242.4 Å		0.81 Å/pix.
x 300 pix.
= 242.4 Å		0.81 Å/pix.
x 300 pix.
= 242.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.808 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 2.8
Minimum - Maximum-6.2025876 - 12.614324999999999
Average (Standard dev.)0.096850306 (±0.9126954)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 242.40001 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: half map 2

Fileemd_50442_half_map_1.map
Annotationhalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half map 1

Fileemd_50442_half_map_2.map
Annotationhalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : amyloid-beta fibrils

EntireName: amyloid-beta fibrils
Components
  • Tissue: amyloid-beta fibrils
    • Protein or peptide: amyloid-beta

-
Supramolecule #1: amyloid-beta fibrils

SupramoleculeName: amyloid-beta fibrils / type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: amyloid-beta

MacromoleculeName: amyloid-beta / type: protein_or_peptide / ID: 1
Details: It is not clear whether the sequence is that of human WT amyloid-beta or the Uppsala variant AbetaUpp(1-42)delta(19-24).
Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
SequenceString:
UNK

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / 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: 3.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 2.45 Å
Applied symmetry - Helical parameters - Δ&Phi: 178.4 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 5.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3) / Number images used: 5023
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Details: an initial 3D reference was computed de novo from multiple 2D class averages assuming a helical rise of 4.75 Ang and a twist value calculated from the crossover-distance of each fibril ...Details: an initial 3D reference was computed de novo from multiple 2D class averages assuming a helical rise of 4.75 Ang and a twist value calculated from the crossover-distance of each fibril observed from the larger box 2D class averages using the relion_helix_inimodel2d command
Final angle assignmentType: NOT APPLICABLE
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