登録情報 データベース : EMDB / ID : EMD-44386 ダウンロードとリンクタイトル Integrin alpha-5 beta-1 in complex with BIIG2 Fab マップデータsharpened map 詳細 試料複合体 : Protein complex of integrin alpha-5 beta-1 with BIIG2 Fabタンパク質・ペプチド : Integrin alpha-5 light chainタンパク質・ペプチド : Integrin beta-1タンパク質・ペプチド : BIIG2 Fab Heavy Chainタンパク質・ペプチド : BIIG2 Fab Light Chainリガンド : CALCIUM IONリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 詳細 キーワード Integrin / Antibody Fab / Inhibitory / SIGNALING PROTEIN / CELL ADHESION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 alpha8-beta1 complex / integrin alpha3-beta1 complex / integrin alpha5-beta1 complex / integrin alpha6-beta1 complex / integrin alpha7-beta1 complex / integrin alpha10-beta1 complex / integrin alpha11-beta1 complex / positive regulation of glutamate uptake involved in transmission of nerve impulse / myoblast fate specification / integrin alpha9-beta1 complex ... integrin alpha8-beta1 complex / integrin alpha3-beta1 complex / integrin alpha5-beta1 complex / integrin alpha6-beta1 complex / integrin alpha7-beta1 complex / integrin alpha10-beta1 complex / integrin alpha11-beta1 complex / positive regulation of glutamate uptake involved in transmission of nerve impulse / myoblast fate specification / integrin alpha9-beta1 complex / regulation of collagen catabolic process / cardiac cell fate specification / integrin alpha1-beta1 complex / integrin binding involved in cell-matrix adhesion / integrin alpha4-beta1 complex / cell-cell adhesion mediated by integrin / collagen binding involved in cell-matrix adhesion / integrin alpha2-beta1 complex / reactive gliosis / Localization of the PINCH-ILK-PARVIN complex to focal adhesions / formation of radial glial scaffolds / Other semaphorin interactions / cerebellar climbing fiber to Purkinje cell synapse / Formation of the ureteric bud / myelin sheath abaxonal region / CD40 signaling pathway / calcium-independent cell-matrix adhesion / Fibronectin matrix formation / positive regulation of fibroblast growth factor receptor signaling pathway / regulation of synapse pruning / integrin alphav-beta1 complex / CHL1 interactions / basement membrane organization / RUNX2 regulates genes involved in cell migration / cardiac muscle cell myoblast differentiation / MET interacts with TNS proteins / alphav-beta3 integrin-vitronectin complex / Laminin interactions / cardiac muscle cell differentiation / Platelet Adhesion to exposed collagen / germ cell migration / leukocyte tethering or rolling / vascular endothelial growth factor receptor 2 binding / cell projection organization / myoblast fusion / positive regulation of vascular endothelial growth factor signaling pathway / Elastic fibre formation / mesodermal cell differentiation / cell-substrate junction assembly / platelet-derived growth factor receptor binding / myoblast differentiation / axon extension / cell migration involved in sprouting angiogenesis / Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin / positive regulation of vascular endothelial growth factor receptor signaling pathway / central nervous system neuron differentiation / positive regulation of cell-substrate adhesion / regulation of spontaneous synaptic transmission / heterophilic cell-cell adhesion / wound healing, spreading of epidermal cells / epidermal growth factor receptor binding / positive regulation of fibroblast migration / integrin complex / lamellipodium assembly / sarcomere organization / heterotypic cell-cell adhesion / MET activates PTK2 signaling / Basigin interactions / Molecules associated with elastic fibres / negative regulation of vasoconstriction / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / leukocyte cell-cell adhesion / muscle organ development / Syndecan interactions / cell adhesion mediated by integrin / positive regulation of wound healing / dendrite morphogenesis / negative regulation of neuron differentiation / positive regulation of neuroblast proliferation / negative regulation of Rho protein signal transduction / response to muscle activity / maintenance of blood-brain barrier / positive regulation of sprouting angiogenesis / cell-substrate adhesion / homophilic cell-cell adhesion / endodermal cell differentiation / TGF-beta receptor signaling activates SMADs / cleavage furrow / establishment of mitotic spindle orientation / fibronectin binding / negative regulation of anoikis / intercalated disc / cellular response to low-density lipoprotein particle stimulus / positive regulation of GTPase activity / RHOG GTPase cycle / glial cell projection / neuroblast proliferation / RAC2 GTPase cycle / RAC3 GTPase cycle / ECM proteoglycans 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 tail domain / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrin beta subunit, tail ... Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta tail domain / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily / Integrin_B_tail / EGF-like domain, extracellular / EGF-like domain / Integrins beta chain EGF (I-EGF) domain profile. / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain EGF (I-EGF) domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / Integrins alpha chain signature. / Integrin alpha chain / Integrin alpha beta-propellor / : / Integrin alpha Ig-like domain 2 / 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 / von Willebrand factor A-like domain superfamily / EGF-like domain signature 1. 類似検索 - ドメイン・相同性生物種 Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.6 Å 詳細 データ登録者Nguyen A / Azumaya CM / Campbell MG 資金援助 米国, 3件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35 GM147414-01 米国 The Pew Charitable Trusts 米国 Other private P30 CA015704-40
引用ジャーナル : bioRxiv / 年 : 2025タイトル : Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.著者 : Adam Nguyen / Joel B Heim / Gabriele Cordara / Matthew C Chan / Hedda Johannesen / Cristine Charlesworth / Ming Li / Caleigh M Azumaya / Benjamin Madden / Ute Krengel / Alexander Meves / Melody G Campbell / 要旨 : Integrins are heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1 is a key mediator of angiogenesis and its dysregulation is associated with tumor progression and ... Integrins are heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1 is a key mediator of angiogenesis and its dysregulation is associated with tumor progression and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful due to poor efficacy and off-target effects. A contributing factor is our limited understanding of how integrin conformation influences interactions with therapeutics. Using cell-based functional assays, patient derived xenografts, biophysics, and electron microscopy, we shed light on these relationships by characterizing two anti-α5β1 antibodies, BIIG2 and MINT1526A. We show that both antibodies bind α5β1 with nanomolar affinity, reduce angiogenesis , and bind overlapping epitopes that block fibronectin binding. However, using cryoEM, we reveal that while BIIG2 binding doesn't alter the conformational states, MINT1526A restricts α5β1's range of flexibility. These insights can guide which aspects to prioritize and improve the design of future integrin-targeted therapeutics. 履歴 登録 2024年4月2日 - ヘッダ(付随情報) 公開 2025年2月5日 - マップ公開 2025年2月5日 - 更新 2025年10月22日 - 現状 2025年10月22日 処理サイト : RCSB / 状態 : 公開
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