[English] 日本語
Yorodumi
- EMDB-25133: Androgen receptor bound to DNA - Splayed state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-25133
TitleAndrogen receptor bound to DNA - Splayed state
Map data
Sample
  • Complex: Androgen receptor bound to DNA - Splayed state
    • DNA: ARE DNA
    • Protein or peptide: Androgen receptor
Biological speciesMus musculus (house mouse) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 9.1 Å
AuthorsWasmuth EV / Vanden Broeck A / Klinge S / Sawyers CL
Funding support United States, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM140264 United States
Department of Defense (DOD, United States)W81XWH-18-1-0182 United States
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Mol Cell / Year: 2022
Title: Allosteric interactions prime androgen receptor dimerization and activation.
Authors: Elizabeth V Wasmuth / Arnaud Vanden Broeck / Justin R LaClair / Elizabeth A Hoover / Kayla E Lawrence / Navid Paknejad / Kyrie Pappas / Doreen Matthies / Biran Wang / Weiran Feng / Philip A ...Authors: Elizabeth V Wasmuth / Arnaud Vanden Broeck / Justin R LaClair / Elizabeth A Hoover / Kayla E Lawrence / Navid Paknejad / Kyrie Pappas / Doreen Matthies / Biran Wang / Weiran Feng / Philip A Watson / John C Zinder / Wouter R Karthaus / M Jason de la Cruz / Richard K Hite / Katia Manova-Todorova / Zhiheng Yu / Susan T Weintraub / Sebastian Klinge / Charles L Sawyers /
Abstract: The androgen receptor (AR) is a nuclear receptor that governs gene expression programs required for prostate development and male phenotype maintenance. Advanced prostate cancers display AR ...The androgen receptor (AR) is a nuclear receptor that governs gene expression programs required for prostate development and male phenotype maintenance. Advanced prostate cancers display AR hyperactivation and transcriptome expansion, in part, through AR amplification and interaction with oncoprotein cofactors. Despite its biological importance, how AR domains and cofactors cooperate to bind DNA has remained elusive. Using single-particle cryo-electron microscopy, we isolated three conformations of AR bound to DNA, showing that AR forms a non-obligate dimer, with the buried dimer interface utilized by ancestral steroid receptors repurposed to facilitate cooperative DNA binding. We identify novel allosteric surfaces which are compromised in androgen insensitivity syndrome and reinforced by AR's oncoprotein cofactor, ERG, and by DNA-binding motifs. Finally, we present evidence that this plastic dimer interface may have been adopted for transactivation at the expense of DNA binding. Our work highlights how fine-tuning AR's cooperative interactions translate to consequences in development and disease.
History
DepositionOct 11, 2021-
Header (metadata) releaseMay 4, 2022-
Map releaseMay 4, 2022-
UpdateJun 22, 2022-
Current statusJun 22, 2022Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_25133.png

Downloads & links

-
Map

FileDownload / File: emd_25133.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 2.138 Å
Density
Contour LevelBy AUTHOR: 0.037
Minimum - Maximum-0.031414554 - 0.21738802
Average (Standard dev.)0.0010353605 (±0.007160771)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 273.664 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_25133_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_25133_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Androgen receptor bound to DNA - Splayed state

EntireName: Androgen receptor bound to DNA - Splayed state
Components
  • Complex: Androgen receptor bound to DNA - Splayed state
    • DNA: ARE DNA
    • Protein or peptide: Androgen receptor

-
Supramolecule #1: Androgen receptor bound to DNA - Splayed state

SupramoleculeName: Androgen receptor bound to DNA - Splayed state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)

-
Macromolecule #1: ARE DNA

MacromoleculeName: ARE DNA / type: dna / ID: 1 / Classification: DNA
Source (natural)Organism: Homo sapiens (human)
SequenceString:
TAGCGTGGCC AGAACATCAT GTTCTCCGGT GCGAT

-
Macromolecule #2: Androgen receptor

MacromoleculeName: Androgen receptor / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: GSDYYFPPQK TCLICGDEAS GCHYGALTCG SCKVFFKRAA EGKQKYL CA SRNDCTIDKF RRKNCPSCRL RKCYEAGMTL GARKLKKLGN LKLQEEGENS NAGSPTEDPS QKMTVSHI E GYECQPIFLN VLEAIEPGVV CAGHDNNQPD SFAALLSSLN ELGERQLVHV ...String:
GSDYYFPPQK TCLICGDEAS GCHYGALTCG SCKVFFKRAA EGKQKYL CA SRNDCTIDKF RRKNCPSCRL RKCYEAGMTL GARKLKKLGN LKLQEEGENS NAGSPTEDPS QKMTVSHI E GYECQPIFLN VLEAIEPGVV CAGHDNNQPD SFAALLSSLN ELGERQLVHV VKWAKALPGF RNLHVDDQM AVIQYSWMGL MVFAMGWRSF TNVNSRMLYF APDLVFNEYR MHKSRMYSQC VRMRHLSQEF GWLQITPQEF LCMKALLLF SIIPVDGLKN QKFFDELRMN YIKELDRIIA CKRKNPTSCS RRFYQLTKLL DSVQPIAREL H QFTFDLLI KSHMVSVDFP EMMAEIISVQ VPKILSGKVK PIYFHTQ

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE / 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 / Cs: 2.7 mm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 61.27 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Particle selectionNumber selected: 17798
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 9.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 53169
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