登録情報 データベース : EMDB / ID : EMD-18374 ダウンロードとリンクタイトル cryo-EM structure complex of Frizzled-7 and Clostridioides difficile toxin B マップデータ 詳細 試料複合体 : Complex of Frizzled-7 and Clostridioides difficile toxin B細胞器官・細胞要素 : masked region--CROP domain細胞器官・細胞要素 : masked region-core domain細胞器官・細胞要素 : masked region-FZD7 CRD and leg of TcdBリガンド : ZINC ION 詳細 キーワード micriobiology / class F G protein-coupled receptors / CROP dynamics / TOXIN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 ectodermal cell fate specification / negative regulation of cardiac muscle cell differentiation / somatic stem cell division / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / Wnt receptor activity / non-canonical Wnt signaling pathway / mesenchymal to epithelial transition / positive regulation of epithelial cell proliferation involved in wound healing / Wnt-protein binding / glucosyltransferase activity ... negative regulation of ectodermal cell fate specification / negative regulation of cardiac muscle cell differentiation / somatic stem cell division / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / Wnt receptor activity / non-canonical Wnt signaling pathway / mesenchymal to epithelial transition / positive regulation of epithelial cell proliferation involved in wound healing / Wnt-protein binding / glucosyltransferase activity / WNT5:FZD7-mediated leishmania damping / frizzled binding / PCP/CE pathway / Class B/2 (Secretin family receptors) / regulation of canonical Wnt signaling pathway / Wnt signaling pathway, planar cell polarity pathway / host cell cytosol / 転移酵素; グリコシル基を移すもの; 六炭糖残基を移すもの / stem cell population maintenance / negative regulation of cell-substrate adhesion / canonical Wnt signaling pathway / positive regulation of phosphorylation / cellular response to retinoic acid / phosphatidylinositol-4,5-bisphosphate binding / substrate adhesion-dependent cell spreading / cysteine-type peptidase activity / host cell endosome membrane / PDZ domain binding / Asymmetric localization of PCP proteins / positive regulation of JNK cascade / G protein-coupled receptor activity / recycling endosome membrane / neuron differentiation / T cell differentiation in thymus / toxin activity / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ / positive regulation of MAPK cascade / intracellular membrane-bounded organelle / lipid binding / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / host cell plasma membrane / proteolysis / extracellular region / metal ion binding / membrane / plasma membrane 類似検索 - 分子機能 Frizzled-7, cysteine-rich Wnt-binding domain / TcdA/TcdB toxin, N-terminal helical domain / TcdB toxin N-terminal helical domain / TcdA/TcdB toxin, catalytic glycosyltransferase domain / TcdA/TcdB catalytic glycosyltransferase domain / TcdA/TcdB toxin, pore forming domain / TcdA/TcdB pore forming domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region ... Frizzled-7, cysteine-rich Wnt-binding domain / TcdA/TcdB toxin, N-terminal helical domain / TcdB toxin N-terminal helical domain / TcdA/TcdB toxin, catalytic glycosyltransferase domain / TcdA/TcdB catalytic glycosyltransferase domain / TcdA/TcdB toxin, pore forming domain / TcdA/TcdB pore forming domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / CGT/MARTX, cysteine protease (CPD) domain / CGT/MARTX, cysteine protease (CPD) domain superfamily / Peptidase C80 family / CGT/MARTX cysteine protease (CPD) domain profile. / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / Choline-binding repeat / Putative cell wall binding repeat / Cell wall/choline-binding repeat / Cell wall-binding repeat profile. / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / Nucleotide-diphospho-sugar transferases 類似検索 - ドメイン・相同性生物種 Spodoptera frugiperda (ツマジロクサヨトウ) / Priestia megaterium DSM 319 (バクテリア) / Clostridioides difficile (バクテリア) / 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 : 3.26 Å 詳細 データ登録者Kinsolving J / Bous J 資金援助 スウェーデン, デンマーク, 11件 詳細 詳細を隠すOrganization Grant number 国 Swedish Research Council 2019-01190 スウェーデン Cancerfonden 20 1102 PjF スウェーデン Novo Nordisk Foundation NNF21OC0070008 デンマーク Novo Nordisk Foundation NNF22OC0078104 デンマーク Other government 2018-01562 Swedish Research Council 2022-03681 スウェーデン Swedish Research Council 2018-03406 スウェーデン Cancerfonden 20 1287 PjF スウェーデン Swedish Research Council 2022-01398 スウェーデン Cancerfonden 20 0264 PjF スウェーデン Other government 2021-00430 スウェーデン
引用ジャーナル : Cell Rep / 年 : 2024タイトル : Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD.著者 : Julia Kinsolving / Julien Bous / Pawel Kozielewicz / Sara Košenina / Rawan Shekhani / Lukas Grätz / Geoffrey Masuyer / Yuankai Wang / Pål Stenmark / Min Dong / Gunnar Schulte / 要旨 : The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible ... The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible for pathogenesis associated with Clostridioides difficile infection. We employ a live-cell assay examining the affinity between full-length FZDs and TcdB. Moreover, we present cryoelectron microscopy structures of TcdB alone and in complex with full-length FZD, which reveal that large structural rearrangements of the combined repetitive polypeptide domain are required for interaction with FZDs and other TcdB receptors, constituting a first step for receptor recognition. Furthermore, we show that bezlotoxumab, an FDA-approved monoclonal antibody to treat Clostridioides difficile infection, favors the apo-TcdB structure and thus disrupts binding with FZD. The dynamic transition between the two conformations of TcdB also governs the stability of the pore-forming region. Thus, our work provides structural and functional insight into how conformational dynamics of TcdB determine receptor binding. 履歴 登録 2023年9月1日 - ヘッダ(付随情報) 公開 2024年3月20日 - マップ公開 2024年3月20日 - 更新 2024年11月6日 - 現状 2024年11月6日 処理サイト : PDBe / 状態 : 公開
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