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基本情報
登録情報 | データベース: PDB / ID: 8tqw | |||||||||||||||||||||||||||||||||
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タイトル | Structure of human transcriptional Mediator complex | |||||||||||||||||||||||||||||||||
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![]() | TRANSCRIPTION / Mediator / CDK8 / MED12 / MED13 / CKM. | |||||||||||||||||||||||||||||||||
機能・相同性 | ![]() axis elongation involved in somitogenesis / positive regulation of T cell extravasation / embryonic neurocranium morphogenesis / CKM complex / negative regulation of smooth muscle cell differentiation / enucleate erythrocyte development / regulation of RNA biosynthetic process / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition ...axis elongation involved in somitogenesis / positive regulation of T cell extravasation / embryonic neurocranium morphogenesis / CKM complex / negative regulation of smooth muscle cell differentiation / enucleate erythrocyte development / regulation of RNA biosynthetic process / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition / retinal pigment epithelium development / G0 to G1 transition / mammary gland branching involved in thelarche / thyroid hormone receptor signaling pathway / core mediator complex / regulation of vitamin D receptor signaling pathway / post-anal tail morphogenesis / nuclear retinoic acid receptor binding / endoderm development / embryonic brain development / ventricular trabecula myocardium morphogenesis / mediator complex / positive regulation of keratinocyte differentiation / thyroid hormone generation / Generic Transcription Pathway / oligodendrocyte development / peroxisome proliferator activated receptor binding / embryonic heart tube development / cellular response to thyroid hormone stimulus / positive regulation of hepatocyte proliferation / nuclear vitamin D receptor binding / [RNA-polymerase]-subunit kinase / embryonic hindlimb morphogenesis / nuclear thyroid hormone receptor binding / lens development in camera-type eye / limb development / Wnt signaling pathway, planar cell polarity pathway / embryonic hemopoiesis / triglyceride homeostasis / cyclin-dependent protein serine/threonine kinase regulator activity / megakaryocyte development / cellular response to hepatocyte growth factor stimulus / cellular response to steroid hormone stimulus / cortical actin cytoskeleton / positive regulation of intracellular estrogen receptor signaling pathway / histone acetyltransferase binding / LBD domain binding / spinal cord development / epithelial cell proliferation involved in mammary gland duct elongation / RSV-host interactions / erythrocyte development / fat cell differentiation / mammary gland branching involved in pregnancy / monocyte differentiation / skeletal muscle cell differentiation / general transcription initiation factor binding / blastocyst development / somatic stem cell population maintenance / negative regulation of Notch signaling pathway / animal organ regeneration / negative regulation of neuron differentiation / hematopoietic stem cell differentiation / ubiquitin ligase complex / negative regulation of keratinocyte proliferation / cyclin-dependent kinase / positive regulation of transcription initiation by RNA polymerase II / embryonic placenta development / nuclear receptor-mediated steroid hormone signaling pathway / cyclin-dependent protein serine/threonine kinase activity / Schwann cell development / cyclin-dependent protein kinase holoenzyme complex / RNA polymerase II preinitiation complex assembly / negative regulation of fibroblast proliferation / keratinocyte differentiation / lactation / : / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / RNA polymerase II CTD heptapeptide repeat kinase activity / BMAL1:CLOCK,NPAS2 activates circadian expression / Activation of gene expression by SREBF (SREBP) / cellular response to epidermal growth factor stimulus / positive regulation of erythrocyte differentiation / cholesterol homeostasis / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / neural tube closure / transcription initiation at RNA polymerase II promoter / positive regulation of transcription elongation by RNA polymerase II / chromatin DNA binding / mRNA transcription by RNA polymerase II / NOTCH1 Intracellular Domain Regulates Transcription / promoter-specific chromatin binding / liver development / Heme signaling / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Transcriptional activation of mitochondrial biogenesis 類似検索 - 分子機能 | |||||||||||||||||||||||||||||||||
生物種 | ![]() | |||||||||||||||||||||||||||||||||
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: 8.2 Å | |||||||||||||||||||||||||||||||||
![]() | Chen, S.F. / Chao, T.C. / Kim, H.J. / Tang, H.C. / Khadka, S. / Li, T. / Murakami, K. / Boyer, T.G. / Tsai, K.L. | |||||||||||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module. 著者: Ti-Chun Chao / Shin-Fu Chen / Hee Jong Kim / Hui-Chi Tang / Hsiang-Ching Tseng / An Xu / Leon Palao / Subash Khadka / Tao Li / Mo-Fan Huang / Dung-Fang Lee / Kenji Murakami / Thomas G Boyer / Kuang-Lei Tsai / ![]() 要旨: The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex ...The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function. | |||||||||||||||||||||||||||||||||
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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 | ![]() | 2 MB | 表示 | ![]() |
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PDB形式 | ![]() | 1.5 MB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.5 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.7 MB | 表示 | |
XML形式データ | ![]() | 249 KB | 表示 | |
CIF形式データ | ![]() | 405.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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
+Mediator of RNA polymerase II transcription subunit ... , 26種, 26分子 01234ADFGHIJKNOPQRSTUVWXcd
-タンパク質 , 2種, 2分子 ab
#26: タンパク質 | 分子量: 53368.668 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#27: タンパク質 | 分子量: 33279.691 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-タンパク質・ペプチド / 非ポリマー , 2種, 5分子 B

#30: 化合物 | ChemComp-ZN / #7: タンパク質・ペプチド | | 分子量: 1720.111 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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Has protein modification | Y |
-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: The human transcriptional Mediator complex / タイプ: COMPLEX Entity ID: #9, #11, #18, #28-#29, #6, #26, #5, #7, #27, #17, #8, #1, #10, #12-#16, #19-#25, #2-#4 由来: NATURAL |
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由来(天然) | 生物種: ![]() |
緩衝液 | pH: 7.9 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK III / 凍結剤: ETHANE / 湿度: 100 % |
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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: TFS 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): 2800 nm / 最小 デフォーカス(公称値): 600 nm |
撮影 | 電子線照射量: 52 e/Å2 フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
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解析
EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 8.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 6348 / 対称性のタイプ: POINT |