登録情報 データベース : EMDB / ID : EMD-7013 構造の表示 ダウンロードとリンクタイトル Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609 マップデータHuman alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609 詳細 試料複合体 : Quaternary complex of human alpha-V beta-3 integrin with the Fab LM609タンパク質・ペプチド : Integrin alpha-V Integrin alpha Vタンパク質・ペプチド : Integrin beta-3 Integrin beta 3タンパク質・ペプチド : Fab LM609 heavy chainタンパク質・ペプチド : Fab LM609 light chain 詳細 キーワード alpha-V beta-3 integrin / LM609 / vitaxin / abegrin / SIGNALING PROTEIN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
integrin alphav-beta6 complex / integrin alphav-beta8 complex / 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 ... integrin alphav-beta6 complex / integrin alphav-beta8 complex / 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 / tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / Laminin interactions / regulation of extracellular matrix organization / platelet alpha granule membrane / positive regulation of glomerular mesangial cell proliferation / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / entry into host cell by a symbiont-containing vacuole / maintenance of postsynaptic specialization structure / fibrinogen binding / alphav-beta3 integrin-HMGB1 complex / blood coagulation, fibrin clot formation / negative regulation of lipid transport / vascular endothelial growth factor receptor 2 binding / glycinergic synapse / negative regulation of low-density lipoprotein receptor activity / regulation of release of sequestered calcium ion into cytosol / angiogenesis involved in wound healing / Elastic fibre formation / regulation of phagocytosis / cell-substrate junction assembly / mesodermal cell differentiation / transforming growth factor beta binding / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / positive regulation of small GTPase mediated signal transduction / filopodium membrane / extracellular matrix binding / positive regulation of fibroblast migration / regulation of postsynaptic neurotransmitter receptor internalization / positive regulation of vascular endothelial growth factor receptor signaling pathway / apolipoprotein A-I-mediated signaling pathway / regulation of bone resorption / apoptotic cell clearance / wound healing, spreading of epidermal cells / positive regulation of cell adhesion mediated by integrin / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / positive regulation of intracellular signal transduction / positive regulation of cell-matrix adhesion / cellular response to insulin-like growth factor stimulus / smooth muscle cell migration / microvillus membrane / cell adhesion mediated by integrin / Syndecan interactions / negative chemotaxis / p130Cas linkage to MAPK signaling for integrins / activation of protein kinase activity / cellular response to platelet-derived growth factor stimulus / cell-substrate adhesion / protein disulfide isomerase activity / positive regulation of smooth muscle cell migration / endodermal cell differentiation / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / GRB2:SOS provides linkage to MAPK signaling for Integrins / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / platelet-derived growth factor receptor signaling pathway / fibronectin binding / positive regulation of cell adhesion / ECM proteoglycans / voltage-gated calcium channel activity / positive regulation of T cell migration / positive regulation of bone resorption / Integrin cell surface interactions / 脈管形成 / coreceptor activity / specific granule membrane / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / phagocytic vesicle / extrinsic apoptotic signaling pathway in absence of ligand / cell adhesion molecule binding / positive regulation of endothelial cell proliferation / ERK1 and ERK2 cascade / 着床 / positive regulation of endothelial cell migration / Integrin signaling / substrate adhesion-dependent cell spreading 類似検索 - 分子機能 Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin beta tail domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily ... Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin beta tail domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily / Integrin_B_tail / 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様ドメイン / 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 domain superfamily / Integrin alpha, N-terminal / PSI domain / domain found in Plexins, Semaphorins and Integrins / von Willebrand factor A-like domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. 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 単粒子再構成法 / ネガティブ染色法 / 解像度 : 35.0 Å 詳細 データ登録者Borst AJ / James ZN 引用ジャーナル : Structure / 年 : 2017タイトル : The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human αβ Integrin via Steric Hindrance.著者 : Andrew J Borst / Zachary M James / William N Zagotta / Mark Ginsberg / Felix A Rey / Frank DiMaio / Marija Backovic / David Veesler / 要旨 : The LM609 antibody specifically recognizes αβ integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II ... The LM609 antibody specifically recognizes αβ integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αβ-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αβ integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αβ. Using single-particle electron microscopy, we show that LM609 binds at the interface between the β-propeller domain of the α chain and the βI domain of the β chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool. 履歴 登録 2017年9月4日 - ヘッダ(付随情報) 公開 2017年11月1日 - マップ公開 2017年11月1日 - 更新 2024年3月13日 - 現状 2024年3月13日 処理サイト : RCSB / 状態 : 公開
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