登録情報 データベース : EMDB / ID : EMD-33572 ダウンロードとリンクタイトル Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 マップデータ 詳細 試料複合体 : Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2タンパク質・ペプチド : Integrin alpha-Vタンパク質・ペプチド : Integrin beta-8タンパク質・ペプチド : Transforming growth factor beta-1 proproteinリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : CALCIUM IONリガンド : MANGANESE (II) ION 詳細機能・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 / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / positive regulation of primary miRNA processing / regulation of branching involved in mammary gland duct morphogenesis / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / frontal suture morphogenesis / negative regulation of skeletal muscle tissue development ... ganglioside metabolic process / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / positive regulation of primary miRNA processing / regulation of branching involved in mammary gland duct morphogenesis / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / frontal suture morphogenesis / negative regulation of skeletal muscle tissue development / regulation of enamel mineralization / regulatory T cell differentiation / regulation of cartilage development / TGFBR2 MSI Frameshift Mutants in Cancer / regulation of blood vessel remodeling / tolerance induction to self antigen / regulation of striated muscle tissue development / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / regulation of protein import into nucleus / embryonic liver development / columnar/cuboidal epithelial cell maturation / type III transforming growth factor beta receptor binding / positive regulation of odontogenesis / Langerhans cell differentiation / negative regulation of hyaluronan biosynthetic process / positive regulation of cardiac muscle cell differentiation / myofibroblast differentiation / positive regulation of receptor signaling pathway via STAT / connective tissue replacement involved in inflammatory response wound healing / positive regulation of exit from mitosis / extracellular matrix assembly / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of macrophage cytokine production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / odontoblast differentiation / opsonin binding / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of smooth muscle cell differentiation / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / integrin alphav-beta1 complex / mammary gland branching involved in thelarche / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / Cross-presentation of particulate exogenous antigens (phagosomes) / retina vasculature development in camera-type eye / heart valve morphogenesis / extracellular matrix protein binding / macrophage derived foam cell differentiation / membrane protein intracellular domain proteolysis / response to laminar fluid shear stress / positive regulation of vasculature development / bronchiole development / hyaluronan catabolic process / ATP biosynthetic process / Laminin interactions / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of extracellular matrix assembly / receptor catabolic process / placenta blood vessel development / lens fiber cell differentiation / negative regulation of extracellular matrix disassembly / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / type II transforming growth factor beta receptor binding / oligodendrocyte development / TGFBR1 LBD Mutants in Cancer / alphav-beta3 integrin-PKCalpha complex / entry into host cell by a symbiont-containing vacuole / response to salt / germ cell migration / negative regulation of biomineral tissue development / positive regulation of mononuclear cell migration / alphav-beta3 integrin-HMGB1 complex / endoderm development / type I transforming growth factor beta receptor binding / phospholipid homeostasis / positive regulation of chemotaxis / negative regulation of lipid transport / negative regulation of myoblast differentiation / positive regulation of endothelial cell apoptotic process / positive regulation of vascular permeability / negative regulation of low-density lipoprotein receptor activity / cell-cell junction organization / regulation of phagocytosis / response to vitamin D / Elastic fibre formation / positive regulation of regulatory T cell differentiation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / response to cholesterol / digestive tract development / negative regulation of interleukin-17 production / surfactant homeostasis / deubiquitinase activator activity / negative regulation of release of sequestered calcium ion into cytosol 類似検索 - 分子機能 Transforming growth factor beta-1 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Transforming growth factor beta, conserved site / TGF-beta family signature. / Transforming growth factor-beta-related / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain ... Transforming growth factor beta-1 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Transforming growth factor beta, conserved site / TGF-beta family signature. / Transforming growth factor-beta-related / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / : / 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 / 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 / Cystine-knot cytokine / 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. / EGF-like domain 類似検索 - ドメイン・相同性 Transforming growth factor beta-1 proprotein / Integrin alpha-V / Integrin beta-8 類似検索 - 構成要素生物種 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 : 3.24 Å 詳細 データ登録者Duan Z / Zhang Z 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 32171201 中国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Specificity of TGF-β1 signal designated by LRRC33 and integrin αβ.著者 : Zelin Duan / Xuezhen Lin / Lixia Wang / Qiuxin Zhen / Yuefeng Jiang / Chuxin Chen / Jing Yang / Chia-Hsueh Lee / Yan Qin / Ying Li / Bo Zhao / Jianchuan Wang / Zhe Zhang / 要旨 : Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger ... Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin αβ/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin αβ and L-TGF-β1, which shows higher avidity and more efficient L-TGF-β1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit β determines its exquisite affinity to L-TGF-β1. Together, our findings provide important insights into the specificity of TGF-β1 signaling achieved by LRRC33 and integrin αβ. 履歴 登録 2022年6月8日 - ヘッダ(付随情報) 公開 2022年8月31日 - マップ公開 2022年8月31日 - 更新 2022年9月7日 - 現状 2022年9月7日 処理サイト : PDBj / 状態 : 公開
すべて表示 表示を減らす