+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7dpa | ||||||
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タイトル | Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex | ||||||
要素 |
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キーワード | SIGNALING PROTEIN / ELMO / DOCK / GEF / GTPASE / RHO / RAC | ||||||
機能・相同性 | 機能・相同性情報 negative regulation of vascular associated smooth muscle contraction / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / podosome assembly / Activated NTRK2 signals through CDK5 / negative regulation of receptor-mediated endocytosis / regulation of hydrogen peroxide metabolic process / ruffle assembly ...negative regulation of vascular associated smooth muscle contraction / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / podosome assembly / Activated NTRK2 signals through CDK5 / negative regulation of receptor-mediated endocytosis / regulation of hydrogen peroxide metabolic process / ruffle assembly / NTRK2 activates RAC1 / Inactivation of CDC42 and RAC1 / NADPH oxidase complex / engulfment of apoptotic cell / WNT5:FZD7-mediated leishmania damping / respiratory burst / guanyl-nucleotide exchange factor complex / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / cortical cytoskeleton organization / hepatocyte growth factor receptor signaling pathway / bone remodeling / myoblast fusion / ruffle organization / thioesterase binding / regulation of stress fiber assembly / negative regulation of fibroblast migration / cell projection assembly / RHO GTPases activate CIT / sphingosine-1-phosphate receptor signaling pathway / Nef and signal transduction / positive regulation of vascular associated smooth muscle cell migration / regulation of nitric oxide biosynthetic process / PCP/CE pathway / podosome / positive regulation of neutrophil chemotaxis / RHO GTPases activate KTN1 / Activation of RAC1 / motor neuron axon guidance / regulation of lamellipodium assembly / Azathioprine ADME / anchoring junction / MET activates RAP1 and RAC1 / positive regulation of cell-substrate adhesion / DCC mediated attractive signaling / Wnt signaling pathway, planar cell polarity pathway / Sema4D mediated inhibition of cell attachment and migration / CD28 dependent Vav1 pathway / Ephrin signaling / lamellipodium assembly / regulation of cell size / establishment or maintenance of cell polarity / DSCAM interactions / Activation of RAC1 downstream of NMDARs / small GTPase-mediated signal transduction / Rho GDP-dissociation inhibitor binding / phagocytosis, engulfment / positive regulation of Rho protein signal transduction / NRAGE signals death through JNK / positive regulation of epithelial cell migration / 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 / EPH-ephrin mediated repulsion of cells / RHO GTPases Activate NADPH Oxidases / RHO GTPases Activate WASPs and WAVEs / localization / RHO GTPases activate IQGAPs / anatomical structure morphogenesis / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / positive regulation of lamellipodium assembly / positive regulation of substrate adhesion-dependent cell spreading / RHO GTPases activate PKNs / regulation of cell migration / positive regulation of microtubule polymerization / positive regulation of stress fiber assembly / GPVI-mediated activation cascade / RAC1 GTPase cycle / EPHB-mediated forward signaling / actin filament polymerization / positive regulation of endothelial cell migration / substrate adhesion-dependent cell spreading / GTPase activator activity / guanyl-nucleotide exchange factor activity / cell-matrix adhesion / cell chemotaxis / small monomeric GTPase / secretory granule membrane / VEGFR2 mediated vascular permeability / G protein activity / Signal transduction by L1 / cell projection / Translocation of SLC2A4 (GLUT4) to the plasma membrane / RHO GTPases Activate Formins / cell motility / regulation of actin cytoskeleton organization / actin filament organization 類似検索 - 分子機能 | ||||||
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: 3.8 Å | ||||||
データ登録者 | Kukimoto-Niino, M. / Katsura, K. / Kaushik, R. / Ehara, H. / Yokoyama, T. / Uchikubo-Kamo, T. / Mishima-Tsumagari, C. / Yonemochi, M. / Ikeda, M. / Hanada, K. ...Kukimoto-Niino, M. / Katsura, K. / Kaushik, R. / Ehara, H. / Yokoyama, T. / Uchikubo-Kamo, T. / Mishima-Tsumagari, C. / Yonemochi, M. / Ikeda, M. / Hanada, K. / Zhang, K.Y.J. / Shirouzu, M. | ||||||
引用 | ジャーナル: Sci Adv / 年: 2021 タイトル: Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex. 著者: Mutsuko Kukimoto-Niino / Kazushige Katsura / Rahul Kaushik / Haruhiko Ehara / Takeshi Yokoyama / Tomomi Uchikubo-Kamo / Reiko Nakagawa / Chiemi Mishima-Tsumagari / Mayumi Yonemochi / Mariko ...著者: Mutsuko Kukimoto-Niino / Kazushige Katsura / Rahul Kaushik / Haruhiko Ehara / Takeshi Yokoyama / Tomomi Uchikubo-Kamo / Reiko Nakagawa / Chiemi Mishima-Tsumagari / Mayumi Yonemochi / Mariko Ikeda / Kazuharu Hanada / Kam Y J Zhang / Mikako Shirouzu / 要旨: The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine ...The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine triphosphatases. Engulfment and cell motility (ELMO) proteins are binding partners of DOCK and regulate Rac activation. Here, we report the cryo-electron microscopy structure of the active ELMO1-DOCK5 complex bound to Rac1 at 3.8-Å resolution. The C-terminal region of ELMO1, including the pleckstrin homology (PH) domain, aids in the binding of the catalytic DOCK homology region 2 (DHR-2) domain of DOCK5 to Rac1 in its nucleotide-free state. A complex α-helical scaffold between ELMO1 and DOCK5 stabilizes the binding of Rac1. Mutagenesis studies revealed that the PH domain of ELMO1 enhances the GEF activity of DOCK5 through specific interactions with Rac1. The structure provides insights into how ELMO modulates the biochemical activity of DOCK and how Rac selectivity is achieved by ELMO. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7dpa.cif.gz | 735 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7dpa.ent.gz | 585.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7dpa.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7dpa_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7dpa_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 7dpa_validation.xml.gz | 134.5 KB | 表示 | |
CIF形式データ | 7dpa_validation.cif.gz | 200.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/dp/7dpa ftp://data.pdbj.org/pub/pdb/validation_reports/dp/7dpa | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 191492.125 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DOCK5 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9H7D0 #2: タンパク質 | 分子量: 20244.258 Da / 分子数: 2 / Mutation: G15A / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RAC1, TC25, MIG5 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P63000, small monomeric GTPase #3: タンパク質 | 分子量: 84337.719 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ELMO1, KIAA0281 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q92556 |
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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 |
-試料調製
構成要素 | 名称: ELMO1-DOCK5-Rac1 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 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: COPPER / 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 | 凍結剤: ETHANE / 湿度: 100 % |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: BRIGHT FIELD / 倍率(補正後): 105000 X / Calibrated defocus min: 0.5 nm / 最大 デフォーカス(補正後): 3 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 2145777 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 149846 / クラス平均像の数: 1 / 対称性のタイプ: POINT |