登録情報 データベース : PDB / ID : 6tgc 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. 要素Dedicator of cytokinesis protein 2 Engulfment and cell motility protein 1 Ras-related C3 botulinum toxin substrate 1 詳細キーワード SIGNALING PROTEIN / guanine nucleotide exchange factor / cytoskeleton / actin / cryoEM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
membrane raft polarization / alpha-beta T cell proliferation / myeloid dendritic cell activation involved in immune response / establishment of T cell polarity / macropinocytosis / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / Activated NTRK2 signals through CDK5 ... membrane raft polarization / alpha-beta T cell proliferation / myeloid dendritic cell activation involved in immune response / establishment of T cell polarity / macropinocytosis / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / Activated NTRK2 signals through CDK5 / immunological synapse formation / negative regulation of receptor-mediated endocytosis / regulation of hydrogen peroxide metabolic process / ruffle assembly / engulfment of apoptotic cell / NTRK2 activates RAC1 / Inactivation of CDC42 and RAC1 / NADPH oxidase complex / negative thymic T cell selection / respiratory burst / WNT5:FZD7-mediated leishmania damping / guanyl-nucleotide exchange factor complex / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / cortical cytoskeleton organization / hepatocyte growth factor receptor signaling pathway / myoblast fusion / ruffle organization / positive thymic T cell selection / thioesterase binding / cell projection assembly / regulation of stress fiber assembly / negative regulation of fibroblast migration / RHO GTPases activate CIT / sphingosine-1-phosphate receptor signaling pathway / Nef and signal transduction / motor neuron axon guidance / PCP/CE pathway / positive regulation of neutrophil chemotaxis / regulation of nitric oxide biosynthetic process / RHO GTPases activate KTN1 / Activation of RAC1 / regulation of lamellipodium assembly / Azathioprine ADME / MET activates RAP1 and RAC1 / DCC mediated attractive signaling / positive regulation of cell-substrate adhesion / regulation of small GTPase mediated signal transduction / Wnt signaling pathway, planar cell polarity pathway / Sema4D mediated inhibition of cell attachment and migration / CD28 dependent Vav1 pathway / Ephrin signaling / lamellipodium assembly / positive regulation of Rho protein signal transduction / establishment or maintenance of cell polarity / regulation of cell size / Activation of RAC1 downstream of NMDARs / small GTPase-mediated signal transduction / Rho GDP-dissociation inhibitor binding / phagocytosis, engulfment / NRAGE signals death through JNK / Rac protein signal transduction / RHO GTPases activate PAKs / positive regulation of focal adhesion assembly / semaphorin-plexin signaling pathway / Sema3A PAK dependent Axon repulsion / ficolin-1-rich granule membrane / RHOG GTPase cycle / RHOA GTPase cycle / RHO GTPases Activate NADPH Oxidases / EPH-ephrin mediated repulsion of cells / RAC2 GTPase cycle / RHO GTPases Activate WASPs and WAVEs / RHO GTPases activate IQGAPs / anatomical structure morphogenesis / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / T cell receptor binding / positive regulation of lamellipodium assembly / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / RHO GTPases activate PKNs / positive regulation of stress fiber assembly / GPVI-mediated activation cascade / positive regulation of microtubule polymerization / EPHB-mediated forward signaling / RAC1 GTPase cycle / regulation of cell migration / actin filament polymerization / positive regulation of endothelial cell migration / GTPase activator activity / substrate adhesion-dependent cell spreading / cell-matrix adhesion / small monomeric GTPase / cell chemotaxis / secretory granule membrane / G protein activity / VEGFR2 mediated vascular permeability / guanyl-nucleotide exchange factor activity / Signal transduction by L1 / Translocation of SLC2A4 (GLUT4) to the plasma membrane / actin filament organization 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 / ELMO domain / ELMO/CED-12 family / ELMO domain profile. / ELMO, armadillo-like helical domain / ELMO, armadillo-like helical domain ... Dedicator of cytokinesis protein 2 / : / Dedicator of cytokinesis, N-terminal domain / Dedicator of cytokinesis, N-terminal, subdomain 1 / DOCK N-terminus / ELMO domain / ELMO/CED-12 family / ELMO domain profile. / ELMO, armadillo-like helical domain / ELMO, armadillo-like helical domain / DOCKER, Lobe A / DOCKER, Lobe B / DOCKER, Lobe C / DHR-2, Lobe C / DHR-2, Lobe B / Dedicator of cytokinesis / C2 DOCK-type domain / DOCKER domain / Dedicator of cytokinesis, C-terminal, lobe A / Dedicator of cytokinesis, C-terminal, lobe C / DHR-2, Lobe A / C2 domain in Dock180 and Zizimin proteins / C2 DOCK-type domain profile. / DOCKER domain profile. / Pleckstrin homology domain / Variant SH3 domain / Small GTPase Rho / small GTPase Rho family 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 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 : 4.1 Å 詳細データ登録者 Chang, L. / Yang, J. / Chang, J.H. / Zhang, Z. / Boland, A. / McLaughlin, S.H. / Abu-Thuraia, A. / Killoran, R.C. / Smith, M.J. / Cote, J.F. / Barford, D. 資金援助 英国, European Union, 3件 詳細 詳細を隠す組織 認可番号 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 登録サイト : PDBE / 処理サイト : PDBE改定 1.0 2020年7月29日 Provider : repository / タイプ : Initial release改定 1.1 2023年5月24日 Group : Database references / Structure summary / カテゴリ : database_2 / structItem : _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct.title改定 1.2 2023年7月26日 Group : Author supporting evidence / Other / カテゴリ : pdbx_audit_support / pdbx_database_statusItem : _pdbx_audit_support.country / _pdbx_database_status.pdb_format_compatible改定 1.3 2024年7月10日 Group : Data collection / カテゴリ : chem_comp_atom / chem_comp_bond / em_admin / Item : _em_admin.last_update
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