[English] 日本語
Yorodumi
- EMDB-40737: FoxP3 forms Ladder-like multimer to bridge TTTG repeats -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-40737
TitleFoxP3 forms Ladder-like multimer to bridge TTTG repeats
Map data
Sample
  • Complex: FoxP3-DNA complex
    • Protein or peptide: Forkhead box protein P3
    • DNA: DNA 72-mer
    • DNA: DNA 72-mer
KeywordsFoxP3 / STRs / transcriptional factor / FKH / TRANSCRIPTION / TRANSCRIPTION-DNA complex
Function / homology
Function and homology information


T cell tolerance induction / positive regulation of peripheral T cell tolerance induction / CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment / tolerance induction / establishment of endothelial blood-brain barrier / positive regulation of CD4-positive, alpha-beta T cell differentiation / negative regulation of alpha-beta T cell proliferation / response to rapamycin / alpha-beta T cell proliferation / negative regulation of interleukin-4 production ...T cell tolerance induction / positive regulation of peripheral T cell tolerance induction / CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment / tolerance induction / establishment of endothelial blood-brain barrier / positive regulation of CD4-positive, alpha-beta T cell differentiation / negative regulation of alpha-beta T cell proliferation / response to rapamycin / alpha-beta T cell proliferation / negative regulation of interleukin-4 production / negative regulation of CREB transcription factor activity / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / negative regulation of T cell cytokine production / transforming growth factor beta1 production / negative regulation of chronic inflammatory response / negative regulation of interleukin-5 production / regulation of isotype switching to IgG isotypes / regulatory T cell differentiation / tolerance induction to self antigen / negative regulation of defense response to virus / T cell mediated immunity / negative regulation of lymphocyte proliferation / negative regulation of T-helper 17 cell differentiation / positive regulation of transforming growth factor beta1 production / T cell anergy / positive regulation of T cell anergy / lymphocyte proliferation / immature T cell proliferation in thymus / positive regulation of T cell tolerance induction / negative regulation of isotype switching to IgE isotypes / isotype switching to IgE isotypes / CD4-positive, alpha-beta T cell differentiation / positive regulation of immature T cell proliferation in thymus / CD4-positive, alpha-beta T cell proliferation / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / regulation of immunoglobulin production / negative regulation of immune response / negative regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of regulatory T cell differentiation / negative regulation of interleukin-17 production / regulation of T cell anergy / myeloid cell homeostasis / negative regulation of cytokine production / negative regulation of NF-kappaB transcription factor activity / negative regulation of interleukin-2 production / histone acetyltransferase binding / negative regulation of interleukin-10 production / NFAT protein binding / positive regulation of interleukin-4 production / B cell homeostasis / negative regulation of interleukin-6 production / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / negative regulation of T cell proliferation / T cell proliferation / T cell activation / response to virus / negative regulation of DNA-binding transcription factor activity / DNA-binding transcription repressor activity, RNA polymerase II-specific / negative regulation of inflammatory response / histone deacetylase binding / transcription corepressor activity / T cell receptor signaling pathway / gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / sequence-specific DNA binding / response to lipopolysaccharide / transcription by RNA polymerase II / DNA-binding transcription factor activity, RNA polymerase II-specific / inflammatory response / chromatin remodeling / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of gene expression / negative regulation of DNA-templated transcription / DNA-templated transcription / positive regulation of gene expression / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol / cytoplasm
Similarity search - Function
: / FOXP, coiled-coil domain / : / FOXP coiled-coil domain / Fork head domain / Forkhead domain / Fork head domain profile. / FORKHEAD / Fork head domain conserved site 2 / Fork head domain signature 2. ...: / FOXP, coiled-coil domain / : / FOXP coiled-coil domain / Fork head domain / Forkhead domain / Fork head domain profile. / FORKHEAD / Fork head domain conserved site 2 / Fork head domain signature 2. / Zinc finger C2H2 type domain signature. / Zinc finger C2H2-type / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
Forkhead box protein P3
Similarity search - Component
Biological speciesMus musculus (house mouse) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsLeng F / Hur S
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Nature / Year: 2023
Title: FOXP3 recognizes microsatellites and bridges DNA through multimerization.
Authors: Wenxiang Zhang / Fangwei Leng / Xi Wang / Ricardo N Ramirez / Jinseok Park / Christophe Benoist / Sun Hur /
Abstract: FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity. However, the molecular ...FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity. However, the molecular mechanisms of FOXP3 remain unclear. Here we here show that FOXP3 uses the forkhead domain-a DNA-binding domain that is commonly thought to function as a monomer or dimer-to form a higher-order multimer after binding to TG repeat microsatellites. The cryo-electron microscopy structure of FOXP3 in a complex with TG repeats reveals a ladder-like architecture, whereby two double-stranded DNA molecules form the two 'side rails' bridged by five pairs of FOXP3 molecules, with each pair forming a 'rung'. Each FOXP3 subunit occupies TGTTTGT within the repeats in a manner that is indistinguishable from that of FOXP3 bound to the forkhead consensus motif (TGTTTAC). Mutations in the intra-rung interface impair TG repeat recognition, DNA bridging and the cellular functions of FOXP3, all without affecting binding to the forkhead consensus motif. FOXP3 can tolerate variable inter-rung spacings, explaining its broad specificity for TG-repeat-like sequences in vivo and in vitro. Both FOXP3 orthologues and paralogues show similar TG repeat recognition and DNA bridging. These findings therefore reveal a mode of DNA recognition that involves transcription factor homomultimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.
History
DepositionMay 5, 2023-
Header (metadata) releaseOct 18, 2023-
Map releaseOct 18, 2023-
UpdateDec 27, 2023-
Current statusDec 27, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_40737.png

Downloads & links

-
Map

FileDownload / File: emd_40737.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.84 Å/pix.
x 400 pix.
= 337.6 Å		0.84 Å/pix.
x 400 pix.
= 337.6 Å		0.84 Å/pix.
x 400 pix.
= 337.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.844 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4
Minimum - Maximum-1.5227193 - 2.9378152
Average (Standard dev.)0.0012691449 (±0.05271806)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 337.6 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_40737_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_40737_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : FoxP3-DNA complex

EntireName: FoxP3-DNA complex
Components
  • Complex: FoxP3-DNA complex
    • Protein or peptide: Forkhead box protein P3
    • DNA: DNA 72-mer
    • DNA: DNA 72-mer

-
Supramolecule #1: FoxP3-DNA complex

SupramoleculeName: FoxP3-DNA complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)

-
Macromolecule #1: Forkhead box protein P3

MacromoleculeName: Forkhead box protein P3 / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 27.282246 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: GSYPLLANGV CKWPGCEKVF EEPEEFLKHC QADHLLDEKG KAQCLLQREV VQSLEQQLEL EKEKLGAMQA HLAGKMALAK APSVASMDK SSCCIVATST QGSVLPAWSA PREAPDGGLF AVRRHLWGSH GNSSFPEFFH NMDYFKYHNM RPPFTYATLI R WAILEAPE ...String:
GSYPLLANGV CKWPGCEKVF EEPEEFLKHC QADHLLDEKG KAQCLLQREV VQSLEQQLEL EKEKLGAMQA HLAGKMALAK APSVASMDK SSCCIVATST QGSVLPAWSA PREAPDGGLF AVRRHLWGSH GNSSFPEFFH NMDYFKYHNM RPPFTYATLI R WAILEAPE RQRTLNEIYH WFTRMFAYFR NHPATWKNAI RHNLSLHKCF VRVESEKGAV WTVDEFEFRK KRSQRPNK

UniProtKB: Forkhead box protein P3

-
Macromolecule #2: DNA 72-mer

MacromoleculeName: DNA 72-mer / type: dna / ID: 2 / Number of copies: 2 / Classification: DNA
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 22.07349 KDa
SequenceString: (DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA) (DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA) (DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC) (DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA)(DA) (DA) (DC)(DA)(DA)(DA)(DC)(DA) ...String:
(DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA) (DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA) (DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC) (DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA)(DA) (DA) (DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA) (DC)(DA)(DA)(DA)(DC)(DA)(DA)(DA)(DC)(DA) (DA)(DA) (DC)(DA)(DA)(DA)(DC)(DA)(DA) (DA)(DC)(DA)(DA)(DA)

-
Macromolecule #3: DNA 72-mer

MacromoleculeName: DNA 72-mer / type: dna / ID: 3 / Number of copies: 2 / Classification: DNA
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 22.307139 KDa
SequenceString: (DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT) (DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG) (DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT) (DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT)(DT) (DG) (DT)(DT)(DT)(DG)(DT)(DT) ...String:
(DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT) (DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG) (DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT) (DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT)(DT) (DG) (DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG) (DT)(DT)(DT)(DG)(DT)(DT)(DT)(DG)(DT)(DT) (DT)(DG) (DT)(DT)(DT)(DG)(DT)(DT)(DT) (DG)(DT)(DT)(DT)(DG)

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7tdx

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 317175
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
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