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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8sro | ||||||
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タイトル | FoxP3 tetramer on TTTG repeats | ||||||
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![]() | TRANSCRIPTION/DNA / FoxP3 / STRs / transcriptional factor / FKH / TRANSCRIPTION / TRANSCRIPTION-DNA complex | ||||||
機能・相同性 | ![]() 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 / negative regulation of chronic inflammatory response / transforming growth factor beta1 production / regulatory T cell differentiation / negative regulation of interleukin-5 production / regulation of isotype switching to IgG isotypes / tolerance induction to self antigen / negative regulation of defense response to virus / negative regulation of lymphocyte proliferation / T cell mediated immunity / 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 proliferation / CD4-positive, alpha-beta T cell differentiation / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / positive regulation of immature T cell proliferation in thymus / 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 immunoglobulin production / regulation of T cell anergy / negative regulation of cytokine production / myeloid cell homeostasis / negative regulation of NF-kappaB transcription factor activity / histone acetyltransferase binding / negative regulation of interleukin-2 production / negative regulation of interleukin-10 production / NFAT protein binding / positive regulation of interleukin-4 production / negative regulation of interleukin-6 production / B cell homeostasis / negative regulation of tumor necrosis factor production / negative regulation of type II interferon 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 / histone deacetylase binding / negative regulation of inflammatory response / transcription corepressor activity / T cell receptor signaling pathway / gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / sequence-specific DNA binding / transcription by RNA polymerase II / response to lipopolysaccharide / DNA-binding transcription factor activity, RNA polymerase II-specific / inflammatory response / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / 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 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() synthetic construct (人工物) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | ||||||
![]() | Leng, F. / Hur, S. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: FOXP3 recognizes microsatellites and bridges DNA through multimerization. 著者: Wenxiang Zhang / Fangwei Leng / Xi Wang / Ricardo N Ramirez / Jinseok Park / Christophe Benoist / Sun Hur / ![]() 要旨: 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. | ||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 131.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 89.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 40736MC ![]() 8srpC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 27282.246 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #2: DNA鎖 | 分子量: 22073.490 Da / 分子数: 2 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) #3: DNA鎖 | 分子量: 22307.139 Da / 分子数: 2 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: FoxP3-DNA complex / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2100 nm / 最小 デフォーカス(公称値): 700 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 317175 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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