登録情報 データベース : EMDB / ID : EMD-10498 構造の表示 ダウンロードとリンクタイトル CryoEM structure of the ternary DOCK2-ELMO1-RAC1 complex マップデータ 詳細 試料複合体 : Ternary complex of DOCK2-ELMO1-RAC1タンパク質・ペプチド : Dedicator of cytokinesis protein 2タンパク質・ペプチド : Engulfment and cell motility protein 1タンパク質・ペプチド : Ras-related C3 botulinum toxin substrate 1 詳細 キーワード guanine nucleotide exchange factor / cytoskeleton / actin / cryoEM / SIGNALING 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
alpha-beta T cell proliferation / membrane raft polarization / myeloid dendritic cell activation involved in immune response / establishment of T cell polarity / embryonic olfactory bulb interneuron precursor migration / anatomical structure arrangement / regulation of ERK5 cascade / angiotensin-activated signaling pathway involved in heart process / cerebral cortex GABAergic interneuron development / regulation of respiratory burst ... alpha-beta T cell proliferation / membrane raft polarization / myeloid dendritic cell activation involved in immune response / establishment of T cell polarity / embryonic olfactory bulb interneuron precursor migration / anatomical structure arrangement / regulation of ERK5 cascade / angiotensin-activated signaling pathway involved in heart process / cerebral cortex GABAergic interneuron development / regulation of respiratory burst / positive regulation of ovarian follicle development / auditory receptor cell morphogenesis / cerebral cortex radially oriented cell migration / localization within membrane / erythrocyte enucleation / regulation of neutrophil migration / negative regulation of interleukin-23 production / macropinocytosis / Activated NTRK2 signals through CDK5 / immunological synapse formation / kinocilium / regulation of cell adhesion involved in heart morphogenesis / interneuron migration / ruffle assembly / engulfment of apoptotic cell / NTRK2 activates RAC1 / Inactivation of CDC42 and RAC1 / NADPH oxidase complex / cochlea morphogenesis / regulation of hydrogen peroxide metabolic process / regulation of neuron maturation / guanyl-nucleotide exchange factor complex / respiratory burst / WNT5:FZD7-mediated leishmania damping / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / cortical cytoskeleton organization / negative thymic T cell selection / positive regulation of skeletal muscle acetylcholine-gated channel clustering / ruffle organization / midbrain dopaminergic neuron differentiation / epithelial cell morphogenesis / GTP-dependent protein binding / positive regulation of bicellular tight junction assembly / cell projection assembly / thioesterase binding / myoblast fusion / positive thymic T cell selection / regulation of lamellipodium assembly / negative regulation of fibroblast migration / regulation of neuron migration / regulation of stress fiber assembly / RHO GTPases activate CIT / cell-cell junction organization / motor neuron axon guidance / Nef and signal transduction / hepatocyte growth factor receptor signaling pathway / PCP/CE pathway / Activation of RAC1 / RHO GTPases activate KTN1 / sphingosine-1-phosphate receptor signaling pathway / regulation of nitric oxide biosynthetic process / MET activates RAP1 and RAC1 / DCC mediated attractive signaling / regulation of small GTPase mediated signal transduction / quinolinate biosynthetic process / Azathioprine ADME / Sema4D mediated inhibition of cell attachment and migration / Ephrin signaling / hyperosmotic response / CD28 dependent Vav1 pathway / positive regulation of neutrophil chemotaxis / Wnt signaling pathway, planar cell polarity pathway / superoxide anion generation / regulation of receptor signaling pathway via JAK-STAT / lamellipodium assembly / phagocytosis, engulfment / NRAGE signals death through JNK / positive regulation of ruffle assembly / dendrite morphogenesis / small GTPase-mediated signal transduction / Rho GDP-dissociation inhibitor binding / Activation of RAC1 downstream of NMDARs / positive regulation of Rho protein signal transduction / positive regulation of dendritic spine development / synaptic transmission, GABAergic / pericentriolar material / positive regulation of actin filament polymerization / establishment or maintenance of cell polarity / Rac protein signal transduction / semaphorin-plexin signaling pathway / RHO GTPases activate PAKs / RHOG GTPase cycle / Sema3A PAK dependent Axon repulsion / ficolin-1-rich granule membrane / EPH-ephrin mediated repulsion of cells / regulation of postsynapse assembly / RHOA GTPase cycle / RAC2 GTPase cycle / positive regulation of focal adhesion assembly / RHO GTPases Activate NADPH Oxidases 類似検索 - 分子機能 Dedicator of cytokinesis protein 2 / Dedicator of cytokinesis, N-terminal domain / Dedicator of cytokinesis, N-terminal, subdomain 1 / : / DOCK N-terminus / Dedicator of cytokinesis (DOCK) TPR region / ELMO domain / ELMO, armadillo-like helical domain / : / ELMO/CED-12 family ... Dedicator of cytokinesis protein 2 / Dedicator of cytokinesis, N-terminal domain / Dedicator of cytokinesis, N-terminal, subdomain 1 / : / DOCK N-terminus / Dedicator of cytokinesis (DOCK) TPR region / ELMO domain / ELMO, armadillo-like helical domain / : / ELMO/CED-12 family / ELMO, armadillo-like helical domain / ELMO domain profile. / Dedicator of cytokinesis / C2 DOCK-type domain / DOCKER domain / Dedicator of cytokinesis, C-terminal, lobe A / Dedicator of cytokinesis, C-terminal, lobe C / DOCKER, Lobe A / DOCKER, Lobe B / DOCKER, Lobe C / DHR-2, Lobe A / C2 domain in Dock180 and Zizimin proteins / DHR-2, Lobe C / DHR-2, Lobe B / C2 DOCK-type domain profile. / DOCKER domain profile. / Pleckstrin homology domain / Variant SH3 domain / Small GTPase Rho / Small GTPase Rho domain profile. / C2 domain superfamily / Pleckstrin homology domain / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Armadillo-like helical / Small GTP-binding protein domain / PH-like domain superfamily / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Ras-related C3 botulinum toxin substrate 1 / Engulfment and cell motility protein 1 / Dedicator of cytokinesis protein 2 類似検索 - 構成要素生物種 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 : 4.1 Å 詳細 データ登録者Chang L / Yang J 資金援助 英国, European Union, 3件 詳細 詳細を隠すOrganization Grant number 国 Medical Research Council (United Kingdom) MC_UP_1201/6 英国 Cancer Research UK C576/A14109 英国 Marie Sklodowska-Curie Actions, FragNET ITN 657725 European Union
引用ジャーナル : Nat Commun / 年 : 2020タイトル : Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state.著者 : Leifu Chang / Jing Yang / Chang Hwa Jo / Andreas Boland / Ziguo Zhang / Stephen H McLaughlin / Afnan Abu-Thuraia / Ryan C Killoran / Matthew J Smith / Jean-Francois Côté / David Barford / 要旨 : DOCK (dedicator of cytokinesis) proteins are multidomain guanine nucleotide exchange factors (GEFs) for RHO GTPases that regulate intracellular actin dynamics. DOCK proteins share catalytic (DOCK) ... DOCK (dedicator of cytokinesis) proteins are multidomain guanine nucleotide exchange factors (GEFs) for RHO GTPases that regulate intracellular actin dynamics. DOCK proteins share catalytic (DOCK) and membrane-associated (DOCK) domains. The structurally-related DOCK1 and DOCK2 GEFs are specific for RAC, and require ELMO (engulfment and cell motility) proteins for function. The N-terminal RAS-binding domain (RBD) of ELMO (ELMO) interacts with RHOG to modulate DOCK1/2 activity. Here, we determine the cryo-EM structures of DOCK2-ELMO1 alone, and as a ternary complex with RAC1, together with the crystal structure of a RHOG-ELMO2 complex. The binary DOCK2-ELMO1 complex adopts a closed, auto-inhibited conformation. Relief of auto-inhibition to an active, open state, due to a conformational change of the ELMO1 subunit, exposes binding sites for RAC1 on DOCK2, and RHOG and BAI GPCRs on ELMO1. Our structure explains how up-stream effectors, including DOCK2 and ELMO1 phosphorylation, destabilise the auto-inhibited state to promote an active GEF. 履歴 登録 2019年11月15日 - ヘッダ(付随情報) 公開 2020年7月29日 - マップ公開 2020年7月29日 - 更新 2024年7月10日 - 現状 2024年7月10日 処理サイト : PDBe / 状態 : 公開
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