登録情報 データベース : PDB / ID : 6ujc 構造の表示 ダウンロードとリンクタイトル Integrin alpha-v beta-8 in complex with the Fabs C6-RGD3 and 11D12v2 要素C6-RGD3 heavy chain Fab C6-RGD3 light chain Fab Integrin alpha-V Integrin beta-8 詳細キーワード SIGNALING PROTEIN/IMMUNE SYSTEM / glycoprotein / adhesion / signaling / SIGNALING PROTEIN-IMMUNE SYSTEM 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
ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / : / opsonin binding ... ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / : / opsonin binding / integrin alphav-beta1 complex / Cross-presentation of particulate exogenous antigens (phagosomes) / extracellular matrix protein binding / Laminin interactions / placenta blood vessel development / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / entry into host cell by a symbiont-containing vacuole / alphav-beta3 integrin-HMGB1 complex / negative regulation of lipid transport / negative regulation of low-density lipoprotein receptor activity / regulation of phagocytosis / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / filopodium membrane / positive regulation of small GTPase mediated signal transduction / extracellular matrix binding / apolipoprotein A-I-mediated signaling pathway / cartilage development / apoptotic cell clearance / wound healing, spreading of epidermal cells / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / positive regulation of intracellular signal transduction / microvillus membrane / negative chemotaxis / cell adhesion mediated by integrin / Syndecan interactions / cell-substrate adhesion / endodermal cell differentiation / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / fibronectin binding / positive regulation of cell adhesion / ECM proteoglycans / voltage-gated calcium channel activity / vasculogenesis / Integrin cell surface interactions / coreceptor activity / specific granule membrane / extrinsic apoptotic signaling pathway in absence of ligand / ERK1 and ERK2 cascade / phagocytic vesicle / substrate adhesion-dependent cell spreading / transforming growth factor beta receptor signaling pathway / cell-matrix adhesion / Signal transduction by L1 / integrin-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / calcium ion transmembrane transport / protein kinase C binding / response to virus / ruffle membrane / VEGFA-VEGFR2 Pathway / cell-cell adhesion / positive regulation of angiogenesis / cell migration / integrin binding / virus receptor activity / positive regulation of cytosolic calcium ion concentration / angiogenesis / protease binding / cell adhesion / positive regulation of cell migration / symbiont entry into host cell / immune response / external side of plasma membrane / negative regulation of gene expression / focal adhesion / positive regulation of cell population proliferation / Neutrophil degranulation / positive regulation of gene expression / cell surface / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol 類似検索 - 分子機能 Integrin domains. Chain A, domain 2 / Integrin alpha, N-terminal / : / Integrin alpha Ig-like domain 3 / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain cysteine-rich domain signature. ... Integrin domains. Chain A, domain 2 / Integrin alpha, N-terminal / : / Integrin alpha Ig-like domain 3 / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain cysteine-rich domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha cytoplasmic region / EGF-like domain, extracellular / EGF-like domain / von Willebrand factor, type A domain / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / : / Integrin alpha Ig-like domain 2 / Integrin alpha chain / Integrin alpha beta-propellor / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / Integrins alpha chain signature. / FG-GAP repeat profile. / Integrin alpha (beta-propellor repeats). / FG-GAP repeat / FG-GAP repeat / Integrin alpha, N-terminal / Integrin domain superfamily / PSI domain / domain found in Plexins, Semaphorins and Integrins / 7 Propeller / Methylamine Dehydrogenase; Chain H / von Willebrand factor A-like domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. / EGF-like domain / Immunoglobulin-like / Sandwich / Rossmann fold / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta 類似検索 - ドメイン・相同性生物種 Homo sapiens (ヒト)Mus musculus (ハツカネズミ)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 : 3.56 Å 詳細データ登録者 Campbell, M.G. / Cormier, A. / Cheng, Y. / Nishimura, S.L. 資金援助 米国, 7件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) U54HL119893 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) R01HL113032 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) R01HL134183 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) R01GM098672 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) S10OD020054 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) S10OD021741 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) P41CA196276 米国
引用ジャーナル : Cell / 年 : 2020タイトル : Cryo-EM Reveals Integrin-Mediated TGF-β Activation without Release from Latent TGF-β.著者 : Melody G Campbell / Anthony Cormier / Saburo Ito / Robert I Seed / Andrew J Bondesson / Jianlong Lou / James D Marks / Jody L Baron / Yifan Cheng / Stephen L Nishimura / 要旨 : Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. ... Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy in cancer. Using cryo-electron microscopy, structure-guided mutagenesis, and cell-based assays, we reveal the binding interactions between the entire αvβ8 ectodomain and its intact natural ligand, L-TGF-β, as well as two different inhibitory antibody fragments to understand the structural underpinnings of αvβ8 binding specificity and TGF-β activation. Our studies reveal a mechanism of TGF-β activation where mature TGF-β signals within the confines of L-TGF-β and the release and diffusion of TGF-β are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit αvβ8-mediated L-TGF-β activation. 履歴 登録 2019年10月2日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2020年2月5日 Provider : repository / タイプ : Initial release改定 1.1 2020年2月19日 Group : Database references / カテゴリ : citation / Item : _citation.journal_volume / _citation.page_first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 / em_entity_assembly / 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 / pdbx_struct_conn_angle / struct_asym / struct_conn / struct_site / struct_site_gen Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _em_entity_assembly.entity_id_list / _entity.formula_weight / _entity.pdbx_description / _entity.pdbx_number_of_molecules / _entity.src_method / _entity.type / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id 解説 : Carbohydrate remediation / Provider : repository / タイプ : Remediation
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