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基本情報
登録情報 | データベース: PDB / ID: 8dp5 | ||||||||||||
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タイトル | Structure of the PEAK3/14-3-3 complex | ||||||||||||
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![]() | SIGNALING PROTEIN / complex / pseudokinase / kinase / adapter | ||||||||||||
機能・相同性 | ![]() negative regulation of peptidyl-serine dephosphorylation / regulation of heart rate by hormone / regulation of potassium ion transmembrane transporter activity / negative regulation of calcium ion transmembrane transporter activity / negative regulation of protein dephosphorylation / membrane repolarization during cardiac muscle cell action potential / cytoplasmic sequestering of protein / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / negative regulation of toll-like receptor signaling pathway / negative regulation of G protein-coupled receptor signaling pathway ...negative regulation of peptidyl-serine dephosphorylation / regulation of heart rate by hormone / regulation of potassium ion transmembrane transporter activity / negative regulation of calcium ion transmembrane transporter activity / negative regulation of protein dephosphorylation / membrane repolarization during cardiac muscle cell action potential / cytoplasmic sequestering of protein / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / negative regulation of toll-like receptor signaling pathway / negative regulation of G protein-coupled receptor signaling pathway / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / regulation of membrane repolarization / protein localization to endoplasmic reticulum / MTOR signalling / NADE modulates death signalling / RAB GEFs exchange GTP for GDP on RABs / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / Signaling by Hippo / vacuolar membrane / negative regulation of calcium ion export across plasma membrane / cytoplasmic pattern recognition receptor signaling pathway / Frs2-mediated activation / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / protein kinase inhibitor activity / positive regulation of catalytic activity / mTORC1-mediated signalling / regulation of heart rate by cardiac conduction / protein localization to nucleus / Regulation of localization of FOXO transcription factors / calcium channel regulator activity / phosphoserine residue binding / Regulation of HSF1-mediated heat shock response / Activation of BAD and translocation to mitochondria / HSF1 activation / potassium channel regulator activity / protein targeting / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / signaling adaptor activity / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / protein sequestering activity / regulation of mitotic cell cycle / regulation of cytosolic calcium ion concentration / substantia nigra development / AURKA Activation by TPX2 / positive regulation of protein export from nucleus / Translocation of SLC2A4 (GLUT4) to the plasma membrane / mitochondrial membrane / hippocampus development / regulation of actin cytoskeleton organization / phosphoprotein binding / TP53 Regulates Metabolic Genes / RAF activation / neuron migration / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / cerebral cortex development / histone deacetylase binding / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / : / Regulation of PLK1 Activity at G2/M Transition / MAPK cascade / Signaling by BRAF and RAF1 fusions / melanosome / actin cytoskeleton / MHC class II protein complex binding / cellular response to heat / regulation of cell shape / scaffold protein binding / protein phosphatase binding / transmembrane transporter binding / protein kinase activity / intracellular signal transduction / cadherin binding / protein heterodimerization activity / protein domain specific binding / focal adhesion / ubiquitin protein ligase binding / perinuclear region of cytoplasm / enzyme binding / endoplasmic reticulum / signal transduction / RNA binding / extracellular exosome / membrane / identical protein binding / nucleus 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: 3.1 Å | ||||||||||||
![]() | Torosyan, H. / Paul, M. / Jura, N. / Verba, K.A. | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3. 著者: Hayarpi Torosyan / Michael D Paul / Antoine Forget / Megan Lo / Devan Diwanji / Krzysztof Pawłowski / Nevan J Krogan / Natalia Jura / Kliment A Verba / ![]() ![]() 要旨: PEAK pseudokinases are molecular scaffolds which dimerize to regulate cell migration, morphology, and proliferation, as well as cancer progression. The mechanistic role dimerization plays in PEAK ...PEAK pseudokinases are molecular scaffolds which dimerize to regulate cell migration, morphology, and proliferation, as well as cancer progression. The mechanistic role dimerization plays in PEAK scaffolding remains unclear, as there are no structures of PEAKs in complex with their interactors. Here, we report the cryo-EM structure of dimeric PEAK3 in complex with an endogenous 14-3-3 heterodimer. Our structure reveals an asymmetric binding mode between PEAK3 and 14-3-3 stabilized by one pseudokinase domain and the SHED domain of the PEAK3 dimer. The binding interface contains a canonical phosphosite-dependent primary interaction and a unique secondary interaction not observed in previous structures of 14-3-3/client complexes. Additionally, we show that PKD regulates PEAK3/14-3-3 binding, which when prevented leads to PEAK3 nuclear enrichment and distinct protein-protein interactions. Altogether, our data demonstrate that PEAK3 dimerization forms an unusual secondary interface for 14-3-3 binding, facilitating 14-3-3 regulation of PEAK3 localization and interactome diversity. | ||||||||||||
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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PDBx/mmCIF形式 | ![]() | 430.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 351.2 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.4 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.4 MB | 表示 | |
XML形式データ | ![]() | 45.2 KB | 表示 | |
CIF形式データ | ![]() | 68.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 27630MC ![]() 8ds6C 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: 52357.031 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | | 分子量: 28114.373 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: タンパク質 | | 分子量: 29208.900 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: タンパク質 | 分子量: 52437.012 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 構成要素の詳細 | The authors state that chains E and P are part of Chains A and B. However, because they cannot ...The authors state that chains E and P are part of Chains A and B. However, because they cannot resolve a large portion of the N-terminal segments of Chain A and B and therefore the connectivity between these two sets of chains, they cannot with confidence assign Chain E residues to Chains A or B and the same with Chain P residues. | 研究の焦点であるリガンドがあるか | N | |
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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: Complex between PEAK3 and 14-3-3 epsilon, beta / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | |||||||||||||||||||||||||
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分子量 | 値: 0.1618 MDa / 実験値: NO | |||||||||||||||||||||||||
由来(天然) | 生物種: ![]() | |||||||||||||||||||||||||
由来(組換発現) | 生物種: ![]() | |||||||||||||||||||||||||
緩衝液 | pH: 7.5 詳細: A final concentration of 0.1% of Octyl-beta-Glucoside (C14H28O6) was added to the sample before freezing. | |||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 1.1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 278.15 K / 詳細: blot time = 7s blot force = 4 |
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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 / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 69 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 169563 / 対称性のタイプ: POINT |