[English] 日本語
Yorodumi
- EMDB-14626: Human elongator Elp456 subcomplex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-14626
TitleHuman elongator Elp456 subcomplex
Map dataHuman Elongator Elp456 hexameric subunit
Sample
  • Complex: Elp4, Elp5, Elp6
KeywordstRNA modification / Elp4 / Elp5 / Elp6 / Elongator Elp456 subcomplex / hexameric ring / TRANSLATION
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.32 Å
AuthorsGaik M / Glatt S
Funding supportEuropean Union, 1 items
OrganizationGrant numberCountry
European Research Council (ERC)101001394European Union
CitationJournal: EMBO Mol Med / Year: 2022
Title: Functional divergence of the two Elongator subcomplexes during neurodevelopment.
Authors: Monika Gaik / Marija Kojic / Megan R Stegeman / Tülay Öncü-Öner / Anna Kościelniak / Alun Jones / Ahmed Mohamed / Pak Yan Stefanie Chau / Sazia Sharmin / Andrzej Chramiec-Głąbik / ...Authors: Monika Gaik / Marija Kojic / Megan R Stegeman / Tülay Öncü-Öner / Anna Kościelniak / Alun Jones / Ahmed Mohamed / Pak Yan Stefanie Chau / Sazia Sharmin / Andrzej Chramiec-Głąbik / Paulina Indyka / Michał Rawski / Anna Biela / Dominika Dobosz / Amanda Millar / Vann Chau / Aycan Ünalp / Michael Piper / Mark C Bellingham / Evan E Eichler / Deborah A Nickerson / Handan Güleryüz / Nour El Hana Abbassi / Konrad Jazgar / Melissa J Davis / Saadet Mercimek-Andrews / Sultan Cingöz / Brandon J Wainwright / Sebastian Glatt /
Abstract: The highly conserved Elongator complex is a translational regulator that plays a critical role in neurodevelopment, neurological diseases, and brain tumors. Numerous clinically relevant variants have ...The highly conserved Elongator complex is a translational regulator that plays a critical role in neurodevelopment, neurological diseases, and brain tumors. Numerous clinically relevant variants have been reported in the catalytic Elp123 subcomplex, while no missense mutations in the accessory subcomplex Elp456 have been described. Here, we identify ELP4 and ELP6 variants in patients with developmental delay, epilepsy, intellectual disability, and motor dysfunction. We determine the structures of human and murine Elp456 subcomplexes and locate the mutated residues. We show that patient-derived mutations in Elp456 affect the tRNA modification activity of Elongator in vitro as well as in human and murine cells. Modeling the pathogenic variants in mice recapitulates the clinical features of the patients and reveals neuropathology that differs from the one caused by previously characterized Elp123 mutations. Our study demonstrates a direct correlation between Elp4 and Elp6 mutations, reduced Elongator activity, and neurological defects. Foremost, our data indicate previously unrecognized differences of the Elp123 and Elp456 subcomplexes for individual tRNA species, in different cell types and in different key steps during the neurodevelopment of higher organisms.
History
DepositionMar 26, 2022-
Header (metadata) releaseJun 15, 2022-
Map releaseJun 15, 2022-
UpdateDec 13, 2023-
Current statusDec 13, 2023Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_14626.png

Downloads & links

-
Map

FileDownload / File: emd_14626.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHuman Elongator Elp456 hexameric subunit
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 320 pix.
= 275.2 Å		0.86 Å/pix.
x 320 pix.
= 275.2 Å		0.86 Å/pix.
x 320 pix.
= 275.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.86 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.255
Minimum - Maximum-0.4732891 - 0.9482441
Average (Standard dev.)0.001801165 (±0.04552566)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 275.2 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_14626_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_14626_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_14626_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Elp4, Elp5, Elp6

EntireName: Elp4, Elp5, Elp6
Components
  • Complex: Elp4, Elp5, Elp6

-
Supramolecule #1: Elp4, Elp5, Elp6

SupramoleculeName: Elp4, Elp5, Elp6 / type: complex / ID: 1 / Parent: 0 / Details: hexameric ring
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 200 KDa

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation state2D array

-
Sample preparation

Concentration0.58 mg/mL
BufferpH: 7.5
Details: 20 mM HEPES pH 7.5, 100 mM NaCl, 2 mM MgCl2, 5 mM DTT
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: OTHER
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Number grids imaged: 1 / Number real images: 11472 / Average electron dose: 41.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

DetailsFrame alignment and dose weighting were performed with MotionCor2 (using Fourier space cropping by a factor of 2, resulting in a pixel size of 1.72), and contrast transfer function was determined with CTFIND4.
Startup modelType of model: INSILICO MODEL
Final reconstructionNumber classes used: 3 / Applied symmetry - Point group: C2 (2 fold cyclic) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 4.32 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 146000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: RANDOM ASSIGNMENT
Final 3D classificationNumber classes: 3 / Software - Name: RELION (ver. 3.1)
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementProtocol: AB INITIO MODEL

+
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