[English] 日本語
Yorodumi
- EMDB-29075: CryoET tomogram of HD patient iPSC-derived neuron (Q77) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-29075
TitleCryoET tomogram of HD patient iPSC-derived neuron (Q77)
Map dataRepresentative IMOD-reconstructed cryoET tomogram of a neurite region in neuron differentiated from induced pluripotent stem cells derived from HD patient with a polyQ tract of length Q=77
Sample
  • Cell: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 77 Qs
Biological speciesHomo sapiens (human)
Methodelectron tomography / cryo EM
AuthorsWu GH / Smith-Geater C / Galaz-Montoya JG / Mitchell PG / Thompson LM / Chiu W
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)P01NS092525 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)S10OD021600 United States
National Institutes of Health/National Institute on Aging (NIH/NIA)R35NS116872 United States
CitationJournal: Nat Commun / Year: 2023
Title: CryoET reveals organelle phenotypes in huntington disease patient iPSC-derived and mouse primary neurons.
Authors: Gong-Her Wu / Charlene Smith-Geater / Jesús G Galaz-Montoya / Yingli Gu / Sanket R Gupte / Ranen Aviner / Patrick G Mitchell / Joy Hsu / Ricardo Miramontes / Keona Q Wang / Nicolette R ...Authors: Gong-Her Wu / Charlene Smith-Geater / Jesús G Galaz-Montoya / Yingli Gu / Sanket R Gupte / Ranen Aviner / Patrick G Mitchell / Joy Hsu / Ricardo Miramontes / Keona Q Wang / Nicolette R Geller / Cathy Hou / Cristina Danita / Lydia-Marie Joubert / Michael F Schmid / Serena Yeung / Judith Frydman / William Mobley / Chengbiao Wu / Leslie M Thompson / Wah Chiu /
Abstract: Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived ...Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD.
History
DepositionDec 13, 2022-
Header (metadata) releaseFeb 22, 2023-
Map releaseFeb 22, 2023-
UpdateFeb 22, 2023-
Current statusFeb 22, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_29075.png

Downloads & links

-
Map

FileDownload / File: emd_29075.map.gz / Format: CCP4 / Size: 2.1 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationRepresentative IMOD-reconstructed cryoET tomogram of a neurite region in neuron differentiated from induced pluripotent stem cells derived from HD patient with a polyQ tract of length Q=77
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
13.76 Å/pix.
x 390 pix.
= 5366.399 Å		13.76 Å/pix.
x 1440 pix.
= 19814.396 Å		13.76 Å/pix.
x 1023 pix.
= 14076.478 Å

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 13.76 Å
Density

Histogram

Histogram (log scale)
Minimum - Maximum-3.0 - 3.0
Average (Standard dev.)-0.0019853546 (±0.97717214)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin143-209209
Dimensions14401023390
Spacing10231440390
CellA: 14076.478 Å / B: 19814.396 Å / C: 5366.399 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : Human neuron differentiated from induced pluripotent stem cells d...

EntireName: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 77 Qs
Components
  • Cell: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 77 Qs

-
Supramolecule #1: Human neuron differentiated from induced pluripotent stem cells d...

SupramoleculeName: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 77 Qs
type: cell / ID: 1 / Parent: 0 / Details: Mitochondria in situ
Source (natural)Organism: Homo sapiens (human) / Strain: CS77iHD77n3 / Organ: Skin / Tissue: Fibroblasts

-
Experimental details

-
Structure determination

Methodcryo EM
Processingelectron tomography
Aggregation statecell

-
Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE
SectioningOther: NO SECTIONING
Fiducial markerManufacturer: Fisher Scientific / Diameter: 15 nm

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 121 / Average electron dose: 1.01 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 5.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Final reconstructionNumber images used: 121

+
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