登録情報 データベース : EMDB / ID : EMD-15781 ダウンロードとリンクタイトル 2C9, C5b9-CD59 cryoEM structure マップデータLocally filtered 2C9-CD59 map 詳細 試料複合体 : 2C9, CD59 inhibited MAC Complex複合体 : CD59 glycoproteinタンパク質・ペプチド : CD59 glycoprotein複合体 : Complement components C5, C6, C7, C8 and C9タンパク質・ペプチド : Complement component C8 beta chainタンパク質・ペプチド : Complement component C8 gamma chainタンパク質・ペプチド : Complement component C8 alpha chainタンパク質・ペプチド : Complement C5タンパク質・ペプチド : Complement component C7タンパク質・ペプチド : Complement component C6タンパク質・ペプチド : Complement component C9 残り3件を表示 表示を減らす 詳細機能・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
negative regulation of activation of membrane attack complex / cell killing / Terminal pathway of complement / membrane attack complex / complement binding / regulation of complement-dependent cytotoxicity / other organism cell membrane / regulation of complement activation / Activation of C3 and C5 / negative regulation of macrophage chemotaxis ... negative regulation of activation of membrane attack complex / cell killing / Terminal pathway of complement / membrane attack complex / complement binding / regulation of complement-dependent cytotoxicity / other organism cell membrane / regulation of complement activation / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / Cargo concentration in the ER / complement activation, alternative pathway / complement activation / chemokine activity / COPII-mediated vesicle transport / retinol binding / endopeptidase inhibitor activity / tertiary granule membrane / positive regulation of vascular endothelial growth factor production / COPI-mediated anterograde transport / specific granule membrane / positive regulation of chemokine production / transport vesicle / endoplasmic reticulum-Golgi intermediate compartment membrane / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / ER to Golgi transport vesicle membrane / protein homooligomerization / chemotaxis / positive regulation of immune response / extracellular vesicle / blood coagulation / G alpha (i) signalling events / in utero embryonic development / vesicle / killing of cells of another organism / cell surface receptor signaling pathway / blood microparticle / inflammatory response / immune response / G protein-coupled receptor signaling pathway / external side of plasma membrane / Golgi membrane / innate immune response / focal adhesion / signaling receptor binding / Neutrophil degranulation / protein-containing complex binding / endoplasmic reticulum membrane / cell surface / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 Kazal-type serine protease inhibitor domain / : / : / Kazal-type serine protease inhibitor domain / Complement component C7, FIM2 N-terminal / Complement component C7, Kazal domain / : / Complement component C6, KAZAL domain / Complement component C8 gamma chain / : ... Kazal-type serine protease inhibitor domain / : / : / Kazal-type serine protease inhibitor domain / Complement component C7, FIM2 N-terminal / Complement component C7, Kazal domain / : / Complement component C6, KAZAL domain / Complement component C8 gamma chain / : / Complement components C8A/B/C6, EGF-like domain / Membrane attack complex component/perforin/complement C9 / Alpha-1-microglobulin / Factor I / membrane attack complex / factor I membrane attack complex / CD59 antigen, conserved site / Membrane attack complex component/perforin domain, conserved site / Membrane attack complex/perforin (MACPF) domain signature. / Ly-6 / u-PAR domain signature. / Ly-6 antigen / uPA receptor -like domain / u-PAR/Ly-6 domain / Ly-6 antigen/uPA receptor-like / : / Complement component 5, CUB domain / membrane-attack complex / perforin / Membrane attack complex/perforin (MACPF) domain profile. / MAC/Perforin domain / Membrane attack complex component/perforin (MACPF) domain / Complement C3/4/5, macroglobulin domain MG1 / Macroglobulin domain MG1 / Anaphylatoxin, complement system domain / Anaphylatoxin domain signature. / Anaphylatoxin, complement system / Anaphylatoxin/fibulin / Anaphylotoxin-like domain / Anaphylatoxin domain profile. / Anaphylatoxin homologous domain / Netrin C-terminal Domain / Kazal domain / Netrin module, non-TIMP type / UNC-6/NTR/C345C module / Kazal domain profile. / Alpha-macroglobulin, receptor-binding / Alpha-macroglobulin, receptor-binding domain superfamily / Macroglobulin domain MG4 / Macroglobulin domain MG3 / A-macroglobulin receptor binding domain / Macroglobulin domain MG4 / Macroglobulin domain MG3 / A-macroglobulin receptor / Netrin domain / NTR domain profile. / Tissue inhibitor of metalloproteinases-like, OB-fold / Alpha-2-macroglobulin / Macroglobulin domain / Alpha-2-macroglobulin, bait region domain / Alpha-macroglobulin-like, TED domain / Alpha-2-macroglobulin family / MG2 domain / A-macroglobulin TED domain / Alpha-2-macroglobulin bait region domain / Alpha-2-Macroglobulin / Alpha-2-macroglobulin family / Thrombospondin type 1 domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / Thrombospondin type-1 (TSP1) repeat superfamily / Thrombospondin type-1 (TSP1) repeat profile. / Thrombospondin type 1 repeats / Thrombospondin type-1 (TSP1) repeat / LDL-receptor class A (LDLRA) domain profile. / Lipocalin family conserved site / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Snake toxin-like superfamily / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / LDL receptor-like superfamily / Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid / Lipocalin / cytosolic fatty-acid binding protein family / Lipocalin/cytosolic fatty-acid binding domain / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. / Calycin / Lipocalin signature. / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Complement C5 / Complement component C9 / Complement component C8 alpha chain / Complement component C8 beta chain / Complement component C8 gamma chain / Complement component C7 / Complement component C6 / CD59 glycoprotein 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / human (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Couves EC / Gardner S / Bubeck D 資金援助 European Union, 英国, 2件 詳細 詳細を隠すOrganization Grant number 国 European Research Council (ERC) No. 864751 European Union Cancer Research UK C24523/A26234 英国
引用ジャーナル : Nat Commun / 年 : 2023タイトル : Structural basis for membrane attack complex inhibition by CD59.著者 : Emma C Couves / Scott Gardner / Tomas B Voisin / Jasmine K Bickel / Phillip J Stansfeld / Edward W Tate / Doryen Bubeck / 要旨 : CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to ... CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 β-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells. 履歴 登録 2022年9月7日 - ヘッダ(付随情報) 公開 2023年2月22日 - マップ公開 2023年2月22日 - 更新 2023年3月1日 - 現状 2023年3月1日 処理サイト : PDBe / 状態 : 公開
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