登録情報 データベース : EMDB / ID : EMD-43927 ダウンロードとリンクタイトル Cryo-EM structure of Phospholipase C epsilon PH-C terminus in complex with RhoA-GTP マップデータ 詳細 試料複合体 : PLCe PH-C in complex with RhoA-GTP複合体 : PH-C fragment (837-2281) of PLC epsilonタンパク質・ペプチド : 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1複合体 : RhoA-GTPタンパク質・ペプチド : Transforming protein RhoAリガンド : CALCIUM IONリガンド : GUANOSINE-5'-TRIPHOSPHATEリガンド : MAGNESIUM ION 詳細 キーワード GPCR signaling / complex / phospholipase / PIP2 hydrolysis / G protein / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
diacylglycerol biosynthetic process / Synthesis of IP3 and IP4 in the cytosol / phosphoinositide phospholipase C / alpha-beta T cell lineage commitment / aortic valve formation / positive regulation of lipase activity / endothelial tube lumen extension / skeletal muscle satellite cell migration / positive regulation of vascular associated smooth muscle contraction / angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure ... diacylglycerol biosynthetic process / Synthesis of IP3 and IP4 in the cytosol / phosphoinositide phospholipase C / alpha-beta T cell lineage commitment / aortic valve formation / positive regulation of lipase activity / endothelial tube lumen extension / skeletal muscle satellite cell migration / positive regulation of vascular associated smooth muscle contraction / angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure / SLIT2:ROBO1 increases RHOA activity / bone trabecula morphogenesis / RHO GTPases Activate Rhotekin and Rhophilins / Roundabout signaling pathway / negative regulation of intracellular steroid hormone receptor signaling pathway / phosphatidylinositol metabolic process / Axonal growth inhibition (RHOA activation) / Axonal growth stimulation / cleavage furrow formation / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / regulation of neural precursor cell proliferation / regulation of osteoblast proliferation / regulation of modification of postsynaptic actin cytoskeleton / forebrain radial glial cell differentiation / mitotic cleavage furrow formation / C-type glycerophospholipase activity / apical junction assembly / negative regulation of cell migration involved in sprouting angiogenesis / glomerulus development / cell junction assembly / beta selection / establishment of epithelial cell apical/basal polarity / cellular response to chemokine / negative regulation of motor neuron apoptotic process / regulation of systemic arterial blood pressure by endothelin / negative regulation of oxidative phosphorylation / regulation of modification of postsynaptic structure / RHO GTPases Activate ROCKs / RHO GTPases activate CIT / negative regulation of cell size / PCP/CE pathway / Sema4D induced cell migration and growth-cone collapse / RHO GTPases activate KTN1 / positive regulation of podosome assembly / positive regulation of alpha-beta T cell differentiation / apolipoprotein A-I-mediated signaling pathway / Sema4D mediated inhibition of cell attachment and migration / wound healing, spreading of cells / PI3K/AKT activation / motor neuron apoptotic process / positive regulation of leukocyte adhesion to vascular endothelial cell / Wnt signaling pathway, planar cell polarity pathway / odontogenesis / ossification involved in bone maturation / regulation of focal adhesion assembly / androgen receptor signaling pathway / negative chemotaxis / EPHA-mediated growth cone collapse / apical junction complex / stress fiber assembly / myosin binding / positive regulation of cytokinesis / RHOC GTPase cycle / regulation of neuron projection development / cellular response to cytokine stimulus / phosphatidylinositol-mediated signaling / cerebral cortex cell migration / positive regulation of protein serine/threonine kinase activity / ERBB2 Regulates Cell Motility / cleavage furrow / semaphorin-plexin signaling pathway / ficolin-1-rich granule membrane / negative regulation of cell-substrate adhesion / RHOA GTPase cycle / mitotic spindle assembly / endothelial cell migration / positive regulation of T cell migration / skeletal muscle tissue development / lipid catabolic process / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / GPVI-mediated activation cascade / Rho protein signal transduction / positive regulation of lamellipodium assembly / RHO GTPases activate PKNs / negative regulation of reactive oxygen species biosynthetic process / positive regulation of stress fiber assembly / release of sequestered calcium ion into cytosol / cytoplasmic microtubule organization / EPHB-mediated forward signaling / positive regulation of neuron differentiation / substrate adhesion-dependent cell spreading / substantia nigra development / guanyl-nucleotide exchange factor activity / regulation of cell migration / secretory granule membrane / cell-matrix adhesion / regulation of microtubule cytoskeleton organization / small monomeric GTPase / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / cell periphery 類似検索 - 分子機能 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 / : / : / Ras association (RalGDS/AF-6) domain / Phosphoinositide phospholipase C family / Phospholipase C, phosphatidylinositol-specific, Y domain / Phosphatidylinositol-specific phospholipase C, Y domain / Phosphatidylinositol-specific phospholipase Y-box domain profile. / Phospholipase C, catalytic domain (part); domain Y / Ras association (RalGDS/AF-6) domain ... 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 / : / : / Ras association (RalGDS/AF-6) domain / Phosphoinositide phospholipase C family / Phospholipase C, phosphatidylinositol-specific, Y domain / Phosphatidylinositol-specific phospholipase C, Y domain / Phosphatidylinositol-specific phospholipase Y-box domain profile. / Phospholipase C, catalytic domain (part); domain Y / Ras association (RalGDS/AF-6) domain / Phosphatidylinositol-specific phospholipase C, X domain / Phosphatidylinositol-specific phospholipase C, X domain / Phospholipase C, catalytic domain (part); domain X / Ras-associating (RA) domain profile. / Phosphatidylinositol-specific phospholipase X-box domain profile. / Ras-associating (RA) domain / Ras guanine nucleotide exchange factor domain superfamily / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / RasGEF domain / Ras guanine-nucleotide exchange factors catalytic domain profile. / Guanine nucleotide exchange factor for Ras-like small GTPases / Ras guanine-nucleotide exchange factors catalytic domain / PLC-like phosphodiesterase, TIM beta/alpha-barrel domain superfamily / Small GTPase Rho / Small GTPase Rho domain profile. / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain / C2 domain profile. / C2 domain superfamily / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / EF-hand domain pair / Small GTP-binding protein domain / Ubiquitin-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Transforming protein RhoA / 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ) / Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.3 Å 詳細 データ登録者Ohri V / Lyon AM 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) 1R01HL141076-01 米国
引用ジャーナル : Commun Biol / 年 : 2025タイトル : RhoA allosterically activates phospholipase Cε via its EF hands.著者 : Vaani Ohri / Kadidia Samassekou / Kaushik Muralidharan / Elisabeth E Garland-Kuntz / Isaac J Fisher / William C Hogan / Bailey M Davis / Angeline M Lyon / 要旨 : Phospholipase Cε (PLCε) cleaves phosphatidylinositol lipids to increase intracellular Ca and activate protein kinase C (PKC) in response to stimulation of cell surface receptors. PLCε is activated ... Phospholipase Cε (PLCε) cleaves phosphatidylinositol lipids to increase intracellular Ca and activate protein kinase C (PKC) in response to stimulation of cell surface receptors. PLCε is activated via direct binding of small GTPases at the cytoplasmic leaflets of cellular membranes. In the cardiovascular system, the RhoA GTPase regulates PLCε to initiate a pathway that protects against ischemia/reperfusion injuries, but the underlying molecular mechanism is not known. We present here the cryo-electron microscopy (cryo-EM) reconstruction of RhoA bound to PLCε, showing that the G protein binds a unique insertion within the PLCε EF hands. Deletion of or mutations to this PLCε insertion decrease RhoA-dependent activation without impacting its regulation by other G proteins. Together, our data support a model wherein RhoA binding to PLCε allosterically activates the lipase and increases its interactions with the membrane, resulting in maximum activity and cardiomyocyte survival. 履歴 登録 2024年3月5日 - ヘッダ(付随情報) 公開 2025年3月12日 - マップ公開 2025年3月12日 - 更新 2025年10月15日 - 現状 2025年10月15日 処理サイト : RCSB / 状態 : 公開
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