登録情報 データベース : EMDB / ID : EMD-53217 ダウンロードとリンクタイトル Structure of the Complement classical and lectin pathway C3 convertase in complex with substrate C3 マップデータSharpened map of Complement C4b2b convertase in complex with substrate C3 詳細 試料複合体 : Classical and lectin pathway C3 convertase in complex with substrate C3タンパク質・ペプチド : Complement C4-Aタンパク質・ペプチド : Complement C2タンパク質・ペプチド : Anti-C4b nanobody B12タンパク質・ペプチド : Complement C3リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : MAGNESIUM ION 詳細 キーワード C3 convertase / Complement classical pathway / convertase-substrate complex / C3 substrate / IMMUNE SYSTEM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
classical-complement-pathway C3/C5 convertase / C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / complement component C1q complex binding / positive regulation of activation of membrane attack complex / response to thyroid hormone / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / Alternative complement activation ... classical-complement-pathway C3/C5 convertase / C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / complement component C1q complex binding / positive regulation of activation of membrane attack complex / response to thyroid hormone / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / Alternative complement activation / complement-mediated synapse pruning / positive regulation of type IIa hypersensitivity / Activation of C3 and C5 / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment / complement activation, GZMK pathway / positive regulation of G protein-coupled receptor signaling pathway / symbiont cell surface / complement-dependent cytotoxicity / positive regulation of D-glucose transmembrane transport / complement receptor mediated signaling pathway / complement activation, alternative pathway / complement activation / Initial triggering of complement / neuron remodeling / endopeptidase inhibitor activity / B cell activation / amyloid-beta clearance / complement activation, classical pathway / positive regulation of vascular endothelial growth factor production / Purinergic signaling in leishmaniasis infection / response to nutrient / Regulation of Complement cascade / Peptide ligand-binding receptors / Post-translational protein phosphorylation / response to bacterium / fatty acid metabolic process / positive regulation of protein phosphorylation / positive regulation of receptor-mediated endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of angiogenesis / azurophil granule lumen / secretory granule lumen / blood microparticle / response to lipopolysaccharide / G alpha (i) signalling events / immune response / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / inflammatory response / receptor ligand activity / serine-type endopeptidase activity / signaling receptor binding / axon / neuronal cell body / Neutrophil degranulation / synapse / dendrite / cell surface / signal transduction / protein-containing complex / proteolysis / : / extracellular exosome / extracellular region / metal ion binding / plasma membrane 類似検索 - 分子機能 : / : / Complement C4, MG1 domain / Complement C4A/B CUB C-terminal domain / Complement B/C2 / Complement C3-like, NTR domain / : / : / Complement component 3, CUB domain, second segment / Complement component 3, CUB domain, first segment ... : / : / Complement C4, MG1 domain / Complement C4A/B CUB C-terminal domain / Complement B/C2 / Complement C3-like, NTR domain / : / : / Complement component 3, CUB domain, second segment / Complement component 3, CUB domain, first segment / Complement C3/4/5, macroglobulin domain MG1 / Macroglobulin domain MG1 / Alpha-2-macroglobulin, conserved site / Alpha-2-macroglobulin family thiolester region signature. / Anaphylatoxin, complement system domain / : / Alpha-macro-globulin thiol-ester bond-forming region / Anaphylatoxin domain signature. / Anaphylatoxin, complement system / Anaphylatoxin/fibulin / Anaphylotoxin-like domain / Anaphylatoxin domain profile. / Anaphylatoxin homologous domain / Netrin C-terminal Domain / Netrin module, non-TIMP type / UNC-6/NTR/C345C module / Macroglobulin domain MG4 / Macroglobulin domain MG4 / Alpha-macroglobulin, receptor-binding / Alpha-macroglobulin, receptor-binding domain superfamily / Macroglobulin domain MG3 / : / A-macroglobulin receptor binding domain / Macroglobulin domain MG3 / A-macroglobulin receptor / Netrin domain / NTR domain profile. / Alpha-2-macroglobulin / Macroglobulin domain / Tissue inhibitor of metalloproteinases-like, OB-fold / 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 / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / von Willebrand factor type A domain / Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid / VWFA domain profile. / von Willebrand factor (vWF) type A domain / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, serine active site. / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Immunoglobulin-like fold / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan 類似検索 - ドメイン・相同性 Complement C3 / Complement C2 / Complement C4-A 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Lama glama (ラマ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.5 Å 詳細 データ登録者De la O Becerra KI / Brondijk THC / Gros P 資金援助 メキシコ, オランダ, European Union, 3件 詳細 詳細を隠すOrganization Grant number 国 Consejo Nacional de Ciencia y Tecnologia (CONACYT) CVU 604718 メキシコ Netherlands Organisation for Scientific Research (NWO) 01.80.104.00 オランダ European Research Council (ERC) 787241 European Union
引用ジャーナル : Nat Commun / 年 : 2025タイトル : Structural insights into C3 convertase activity of the classical pathway of complement.著者 : Karla I De la O Becerra / T Harma C Brondijk / Itziar Serna Martin / Piet Gros / 要旨 : Immune protection by the complement system depends on C3 cleavage by C3 convertases that is critical to all three activation pathways. Structural data on convertase formation in the classical pathway ... Immune protection by the complement system depends on C3 cleavage by C3 convertases that is critical to all three activation pathways. Structural data on convertase formation in the classical pathway and on C3-substrate binding to convertases is lacking. We present the cryo-EM structures of the proconvertase (C4b2), convertase (C4b2b), and convertase-substrate complex (C4b2b-C3) of the classical pathway. The data show that C2 and C4b form proconvertases and convertases like factor B and C3b of the alternative pathway. Substrate C3 binds C4b of the convertase through two interfaces: one also found in the SCIN-inhibited C3bBb dimer, and another facilitated by conformational changes in C3. Bending of C3 and swinging of the C2 protease bring the C3-scissile loop into the active site. The second, charged, C4b-interaction site favors C3- substrate binding, but upon cleavage repels product C3b. Thus, a charge switch-over mechanism effects the catalytic turnover of the convertases producing opsonin C3b. 履歴 登録 2025年3月19日 - ヘッダ(付随情報) 公開 2025年12月24日 - マップ公開 2025年12月24日 - 更新 2026年3月4日 - 現状 2026年3月4日 処理サイト : PDBe / 状態 : 公開
すべて表示 表示を減らす