[English] 日本語
Yorodumi
- EMDB-12549: Paired helical filament from primary age-related tauopathy brain -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-12549
TitlePaired helical filament from primary age-related tauopathy brain
Map dataThe calibrated pixel size was used during post-processing procedures in RELION.
Sample
  • Tissue: Sarkosyl-insoluble fractions from primary age-related tauopathy brain
    • Protein or peptide: Microtubule-associated protein tau
KeywordsTau filament / PROTEIN FIBRIL
Function / homology
Function and homology information


plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / regulation of long-term synaptic depression ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / regulation of long-term synaptic depression / tubulin complex / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / rRNA metabolic process / axonal transport of mitochondrion / regulation of mitochondrial fission / axon development / central nervous system neuron development / intracellular distribution of mitochondria / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / negative regulation of mitochondrial membrane potential / apolipoprotein binding / glial cell projection / axolemma / protein polymerization / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / neurofibrillary tangle assembly / Activation of AMPK downstream of NMDARs / synapse assembly / regulation of cellular response to heat / supramolecular fiber organization / positive regulation of protein localization / regulation of calcium-mediated signaling / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / cytoplasmic microtubule organization / axon cytoplasm / positive regulation of microtubule polymerization / stress granule assembly / phosphatidylinositol binding / regulation of microtubule cytoskeleton organization / nuclear periphery / protein phosphatase 2A binding / positive regulation of superoxide anion generation / cellular response to reactive oxygen species / astrocyte activation / Hsp90 protein binding / microglial cell activation / cellular response to nerve growth factor stimulus / response to lead ion / synapse organization / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / SH3 domain binding / memory / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / neuron projection development / cell-cell signaling / single-stranded DNA binding / protein-folding chaperone binding / actin binding / cellular response to heat / microtubule cytoskeleton / cell body / growth cone / double-stranded DNA binding / microtubule binding / protein-macromolecule adaptor activity / dendritic spine / sequence-specific DNA binding / microtubule / amyloid fibril formation / learning or memory / neuron projection / regulation of autophagy / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding / RNA binding / extracellular region / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Microtubule-associated protein Tau / Microtubule associated protein, tubulin-binding repeat / Tau and MAP protein, tubulin-binding repeat / Tau and MAP proteins tubulin-binding repeat signature. / Tau and MAP proteins tubulin-binding repeat profile. / :
Similarity search - Domain/homology
Microtubule-associated protein tau
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 2.76 Å
AuthorsShi Y / Murzin AG
Funding support United Kingdom, European Union, United States, Japan, 6 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MC_UP_A025_1013 United Kingdom
Medical Research Council (MRC, United Kingdom)MC_U105184291 United Kingdom
Innovative Medicines Initiative116060European Union
National Institutes of Health/National Institute on Aging (NIH/NIA)P30-AG010133 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)U01-NS110437 United States
Japan Agency for Medical Research and Development (AMED)JP20dm0207072 Japan
CitationJournal: Acta Neuropathol / Year: 2021
Title: Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607.
Authors: Yang Shi / Alexey G Murzin / Benjamin Falcon / Alexander Epstein / Jonathan Machin / Paul Tempest / Kathy L Newell / Ruben Vidal / Holly J Garringer / Naruhiko Sahara / Makoto Higuchi / ...Authors: Yang Shi / Alexey G Murzin / Benjamin Falcon / Alexander Epstein / Jonathan Machin / Paul Tempest / Kathy L Newell / Ruben Vidal / Holly J Garringer / Naruhiko Sahara / Makoto Higuchi / Bernardino Ghetti / Ming-Kuei Jang / Sjors H W Scheres / Michel Goedert /
Abstract: Tau and Aβ assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs ...Tau and Aβ assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the β-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.
History
DepositionMar 4, 2021-
Header (metadata) releaseMar 24, 2021-
Map releaseMar 24, 2021-
UpdateJul 10, 2024-
Current statusJul 10, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0212
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.0212
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7nrq
  • Surface level: 0.0212
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7nrq
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_12549.png

Downloads & links

-
Map

FileDownload / File: emd_12549.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThe calibrated pixel size was used during post-processing procedures in RELION.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 330 pix.
= 270.6 Å		0.82 Å/pix.
x 330 pix.
= 270.6 Å		0.82 Å/pix.
x 330 pix.
= 270.6 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: 0.0212 / Movie #1: 0.0212
Minimum - Maximum-0.05333272 - 0.10641742
Average (Standard dev.)0.00043307256 (±0.005208062)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions330330330
Spacing330330330
CellA=B=C: 270.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.820.820.82
M x/y/z330330330
origin x/y/z0.0000.0000.000
length x/y/z270.600270.600270.600
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS330330330
D min/max/mean-0.0530.1060.000

-
Supplemental data

-
Mask #1

Fileemd_12549_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_12549_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_12549_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Sarkosyl-insoluble fractions from primary age-related tauopathy brain

EntireName: Sarkosyl-insoluble fractions from primary age-related tauopathy brain
Components
  • Tissue: Sarkosyl-insoluble fractions from primary age-related tauopathy brain
    • Protein or peptide: Microtubule-associated protein tau

-
Supramolecule #1: Sarkosyl-insoluble fractions from primary age-related tauopathy brain

SupramoleculeName: Sarkosyl-insoluble fractions from primary age-related tauopathy brain
type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Microtubule-associated protein tau

MacromoleculeName: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 45.919871 KDa
SequenceString: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA ...String:
MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP PTREPKKVAV VRTPPKSPSS AK SRLQTAP VPMPDLKNVK SKIGSTENLK HQPGGGKVQI INKKLDLSNV QSKCGSKDNI KHVPGGGSVQ IVYKPVDLSK VTS KCGSLG NIHHKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFRENAKAKT DHGAEIVYKS PVVS GDTSP RHLSNVSSTG SIDMVDSPQL ATLADEVSAS LAKQGL

UniProtKB: Microtubule-associated protein tau

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 2.37 Å
Applied symmetry - Helical parameters - Δ&Phi: 179.44 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 2.76 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 425943
Startup modelType of model: INSILICO MODEL
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