+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7y1t | ||||||
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タイトル | Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 | ||||||
要素 |
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キーワード | SIGNALING PROTEIN | ||||||
機能・相同性 | 機能・相同性情報 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 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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: 3.24 Å | ||||||
データ登録者 | Duan, Z. / Zhang, Z. | ||||||
資金援助 | 中国, 1件
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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 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7y1t.cif.gz | 202 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7y1t.ent.gz | 155.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7y1t.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/y1/7y1t ftp://data.pdbj.org/pub/pdb/validation_reports/y1/7y1t | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 3種, 3分子 ABD
#1: タンパク質 | 分子量: 69812.711 Da / 分子数: 1 / 変異: M401C / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ITGAV / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P06756 |
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#2: タンパク質 | 分子量: 53017.355 Da / 分子数: 1 / 変異: V259C / 由来タイプ: 組換発現 詳細: The first 21 residues (MDMRVPAQLLGLLLLWFSGVL) are signal peptides. 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ITGB8 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P26012 |
#3: タンパク質 | 分子量: 43010.402 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The first 16 residues (MPLLLLLPLLWAGALA) are signal peptides. 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TGFB1, TGFB / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P01137 |
-糖 , 4種, 9分子
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||||
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#5: 多糖 | #6: 多糖 | alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | タイプ: oligosaccharide / 分子量: 1072.964 Da / 分子数: 1 / 由来タイプ: 組換発現 #7: 糖 | ChemComp-NAG / |
-非ポリマー , 2種, 6分子
#8: 化合物 | ChemComp-CA / #9: 化合物 | ChemComp-MN / | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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分子量 | 値: 0.21 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293 |
緩衝液 | pH: 7.5 |
試料 | 濃度: 3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1200 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 60 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア | 名称: SerialEM / カテゴリ: 画像取得 |
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CTF補正 | タイプ: NONE |
3次元再構成 | 解像度: 3.24 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 305011 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: OTHER |