- EMDB-27630: Structure of the PEAK3/14-3-3 complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-27630
タイトル
Structure of the PEAK3/14-3-3 complex
マップデータ
Reconstruction of the PEAK3/14-3-3 complex filtered to 3.1A and sharpened with 107.4 bFactor.
試料
複合体: Complex between PEAK3 and 14-3-3 epsilon, beta
タンパク質・ペプチド: Protein PEAK3
タンパク質・ペプチド: 14-3-3 protein beta/alpha
タンパク質・ペプチド: 14-3-3 protein epsilon
タンパク質・ペプチド: Protein PEAK3 fragment
キーワード
complex / pseudokinase / kinase / adapter / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
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 G protein-coupled receptor signaling pathway / negative regulation of toll-like 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 G protein-coupled receptor signaling pathway / negative regulation of toll-like 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 / positive regulation of catalytic activity / protein kinase inhibitor activity / regulation of heart rate by cardiac conduction / mTORC1-mediated signalling / Regulation of localization of FOXO transcription factors / protein localization to nucleus / calcium channel regulator activity / phosphoserine residue binding / Regulation of HSF1-mediated heat shock response / HSF1 activation / Activation of BAD and translocation to mitochondria / 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 / TP53 Regulates Metabolic Genes / phosphoprotein binding / RAF activation / Signaling by high-kinase activity BRAF mutants / neuron migration / 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 / identical protein binding / membrane / nucleus 類似検索 - 分子機能
National Institutes of Health/National Cancer Institute (NIH/NCI)
U54 CA209891
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM139636
米国
引用
ジャーナル: Nat Commun / 年: 2023 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.