登録情報 データベース : PDB / ID : 6wts 構造の表示 ダウンロードとリンクタイトル CryoEM structure of the C. sordellii lethal toxin TcsL in complex with SEMA6A 要素 詳細 キーワード SIGNALING PROTEIN/TOXIN / cryoEM / signaling protein-toxin complex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 cell adhesion involved in sprouting angiogenesis / negative regulation of sprouting angiogenesis / semaphorin receptor binding / Other semaphorin interactions / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of axon extension involved in axon guidance / positive regulation of neuron migration / chemorepellent activity / neural crest cell migration / host cell cytosol ... negative regulation of cell adhesion involved in sprouting angiogenesis / negative regulation of sprouting angiogenesis / semaphorin receptor binding / Other semaphorin interactions / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of axon extension involved in axon guidance / positive regulation of neuron migration / chemorepellent activity / neural crest cell migration / 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 / negative chemotaxis / glycosyltransferase activity / semaphorin-plexin signaling pathway / cellular response to vascular endothelial growth factor stimulus / cysteine-type peptidase activity / cytoskeleton organization / negative regulation of angiogenesis / host cell endosome membrane / axon guidance / animal organ morphogenesis / negative regulation of ERK1 and ERK2 cascade / nervous system development / toxin activity / cell surface receptor signaling pathway / positive regulation of cell migration / axon / apoptotic process / host cell plasma membrane / extracellular space / extracellular region / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 Semaphorin / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / 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 / CGT/MARTX, cysteine protease (CPD) domain ... Semaphorin / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / 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 / CGT/MARTX, cysteine protease (CPD) domain / CGT/MARTX, cysteine protease (CPD) domain superfamily / Peptidase C80 family / CGT/MARTX cysteine protease (CPD) domain profile. / Choline-binding repeat / Putative cell wall binding repeat / Cell wall/choline-binding repeat / Cell wall-binding repeat profile. / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / PSI domain / domain found in Plexins, Semaphorins and Integrins / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / Nucleotide-diphospho-sugar transferases / WD40/YVTN repeat-like-containing domain superfamily / 2-Layer Sandwich / Mainly Beta / Alpha Beta 類似検索 - ドメイン・相同性生物種 Homo sapiens (ヒト)Paeniclostridium sordellii (バクテリア)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 : 3.3 Å 詳細データ登録者 Kucharska, I. / Rubinstein, J.L. / Julien, J.P. 資金援助 カナダ, 3件 詳細 詳細を隠す組織 認可番号 国 Other government Ontario Early Researcher Awards program カナダ Other government Canada Foundation for Innovation カナダ Other government Ontario Research Fund カナダ
引用ジャーナル : Cell / 年 : 2020タイトル : Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins.著者 : Hunsang Lee / Greg L Beilhartz / Iga Kucharska / Swetha Raman / Hong Cui / Mandy Hiu Yi Lam / Huazhu Liang / John L Rubinstein / Daniel Schramek / Jean-Philippe Julien / Roman A Melnyk / Mikko Taipale / 要旨 : Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome ... Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome associated with gynecological infections. TcsL is 87% similar to C. difficile TcdB, which enters host cells via Frizzled receptors in colon epithelium. However, P. sordellii infections target vascular endothelium, suggesting that TcsL exploits another receptor. Here, using CRISPR/Cas9 screening, we establish semaphorins SEMA6A and SEMA6B as TcsL receptors. We demonstrate that recombinant SEMA6A can protect mice from TcsL-induced edema. A 3.3 Å cryo-EM structure shows that TcsL binds SEMA6A with the same region that in TcdB binds structurally unrelated Frizzled. Remarkably, 15 mutations in this evolutionarily divergent surface are sufficient to switch binding specificity of TcsL to that of TcdB. Our findings establish semaphorins as physiologically relevant receptors for TcsL and reveal the molecular basis for the difference in tissue targeting and disease pathogenesis between highly related toxins. 履歴 登録 2020年5月3日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2020年7月8日 Provider : repository / タイプ : Initial release改定 2.0 2020年7月29日 Group : Atomic model / Data collection ... Atomic model / Data collection / Derived calculations / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_site / struct_site_gen Item : _atom_site.Cartn_x / _atom_site.Cartn_y ... _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _chem_comp.name / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id 解説 : Carbohydrate remediation / Provider : repository / タイプ : Remediation改定 2.1 2020年8月5日 Group : Database references / カテゴリ : citation / Item : _citation.journal_volume / _citation.page_first
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