+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16460 | |||||||||
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タイトル | Cryo-EM Map of the latTGF-beta 28G11 Fab complex | |||||||||
マップデータ | Sharpened map | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 : / positive regulation of primary miRNA processing / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / negative regulation of skeletal muscle tissue development / TGFBR2 MSI Frameshift Mutants in Cancer / regulatory T cell differentiation / regulation of blood vessel remodeling / regulation of striated muscle tissue development / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target ...: / positive regulation of primary miRNA processing / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / negative regulation of skeletal muscle tissue development / TGFBR2 MSI Frameshift Mutants in Cancer / regulatory T cell differentiation / regulation of blood vessel remodeling / 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 / extracellular matrix assembly / embryonic liver development / type III transforming growth factor beta receptor binding / negative regulation of hyaluronan biosynthetic process / positive regulation of cardiac muscle cell differentiation / myofibroblast differentiation / connective tissue replacement involved in inflammatory response wound healing / negative regulation of macrophage cytokine production / odontoblast differentiation / positive regulation of receptor signaling pathway via STAT / TGFBR2 Kinase Domain Mutants in Cancer / : / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / secondary palate development / membrane protein intracellular domain proteolysis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / heart valve morphogenesis / positive regulation of vasculature development / hyaluronan catabolic process / regulation of transforming growth factor beta receptor signaling pathway / ATP biosynthetic process / receptor catabolic process / negative regulation of extracellular matrix disassembly / positive regulation of extracellular matrix assembly / type II transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / positive regulation of chemotaxis / negative regulation of biomineral tissue development / type I transforming growth factor beta receptor binding / cell-cell junction organization / negative regulation of myoblast differentiation / positive regulation of vascular permeability / deubiquitinase activator activity / transforming growth factor beta binding / response to cholesterol / positive regulation of endothelial cell apoptotic process / aortic valve morphogenesis / positive regulation of fibroblast migration / positive regulation of chemokine (C-X-C motif) ligand 2 production / phosphate-containing compound metabolic process / negative regulation of protein localization to plasma membrane / 血管新生 / neural tube development / Molecules associated with elastic fibres / RUNX3 regulates CDKN1A transcription / negative regulation of cytokine production / positive regulation of epidermal growth factor receptor signaling pathway / ventricular cardiac muscle tissue morphogenesis / macrophage derived foam cell differentiation / negative regulation of fat cell differentiation / Syndecan interactions / negative regulation of cell-cell adhesion / positive regulation of interleukin-17 production / TGF-beta receptor signaling activates SMADs / plasma membrane => GO:0005886 / negative regulation of activated T cell proliferation / negative regulation of cell differentiation / positive regulation of SMAD protein signal transduction / RUNX3 regulates p14-ARF / positive regulation of cell division / cellular response to low-density lipoprotein particle stimulus / negative regulation of blood vessel endothelial cell migration / negative regulation of cell cycle / ECM proteoglycans / positive regulation of vascular endothelial growth factor production / positive regulation of collagen biosynthetic process / 上皮間葉転換 / positive regulation of epithelial to mesenchymal transition / positive regulation of blood vessel endothelial cell migration / 脈管形成 / lymph node development / chondrocyte differentiation / hematopoietic progenitor cell differentiation / salivary gland morphogenesis / extrinsic apoptotic signaling pathway / positive regulation of protein dephosphorylation / regulation of cell migration / cellular response to transforming growth factor beta stimulus / antigen binding / positive regulation of protein metabolic process / protein export from nucleus / Downregulation of TGF-beta receptor signaling / 細胞外マトリックス / transforming growth factor beta receptor signaling pathway / positive regulation of superoxide anion generation / negative regulation of miRNA transcription / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 類似検索 - 分子機能 | |||||||||
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: 2.7 Å | |||||||||
データ登録者 | Ebenhoch R / Nar H | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Immunohorizons / 年: 2023 タイトル: Anti-GARP Antibodies Inhibit Release of TGF-β by Regulatory T Cells via Different Modes of Action, but Do Not Influence Their Function In Vitro. 著者: Frederik H Igney / Rebecca Ebenhoch / Felix Schiele / Herbert Nar / 要旨: Regulatory T cells (Treg) play a critical role in controlling immune responses in diseases such as cancer or autoimmunity. Activated Treg express the membrane protein GARP (LRRC32) in complex with ...Regulatory T cells (Treg) play a critical role in controlling immune responses in diseases such as cancer or autoimmunity. Activated Treg express the membrane protein GARP (LRRC32) in complex with the latent form of the immunosuppressive cytokine TGF-β (L-TGF-β). In this study, we confirmed that active TGF-β was generated from its latent form in an integrin-dependent manner and induced TGF-β receptor signaling in activated human Treg. We studied a series of Abs targeting the L-TGF-β/GARP complex with distinct binding modes. We found that TGF-β receptor signaling could be inhibited by anti-TGF-β and by some, but not all, Abs against the L-TGF-β/GARP complex. Cryogenic electron microscopy structures of three L-TGF-β/GARP complex-targeting Abs revealed their distinct epitopes and allowed us to elucidate how they achieve blockade of TGF-β activation. Three different modes of action were identified, including a novel unusual mechanism of a GARP-binding Ab. However, blockade of GARP or TGF-β by Abs did not influence the suppressive activity of human Treg in vitro. We were also not able to confirm a prominent role of GARP in other functions of human Treg, such as FOXP3 induction and Treg stability. These data show that the GARP/TGF-β axis can be targeted pharmacologically in different ways, but further studies are necessary to understand its complexity and to unleash its therapeutic potential. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_16460.map.gz | 8.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-16460-v30.xml emd-16460.xml | 18 KB 18 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_16460.png | 73 KB | ||
その他 | emd_16460_half_map_1.map.gz emd_16460_half_map_2.map.gz | 95.5 MB 95.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16460 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16460 | HTTPS FTP |
-関連構造データ
関連構造データ | 8c7hMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_16460.map.gz / 形式: CCP4 / 大きさ: 8.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Sharpened map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.08 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: Half map B
ファイル | emd_16460_half_map_1.map | ||||||||||||
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注釈 | Half map B | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map A
ファイル | emd_16460_half_map_2.map | ||||||||||||
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注釈 | Half map A | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : latTGF-beta in complex with Fab 28G11
全体 | 名称: latTGF-beta in complex with Fab 28G11 |
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要素 |
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-超分子 #1: latTGF-beta in complex with Fab 28G11
超分子 | 名称: latTGF-beta in complex with Fab 28G11 / タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Transforming growth factor beta-1
分子 | 名称: Transforming growth factor beta-1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 28.531488 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: LSTCKTIDME LVKRKRIEAI RGQILSKLRL ASPPSQGEVP PGPLPEAVLA LYNSTRDRVA GESAEPEPEP EADYYAKEVT RVLMVETHN EIYDKFKQST HSIYMFFNTS ELREAVPEPV LLSRAELRLL RLKLKVEQHV ELYQKYSNNS WRYLSNRLLA P SDSPEWLS ...文字列: LSTCKTIDME LVKRKRIEAI RGQILSKLRL ASPPSQGEVP PGPLPEAVLA LYNSTRDRVA GESAEPEPEP EADYYAKEVT RVLMVETHN EIYDKFKQST HSIYMFFNTS ELREAVPEPV LLSRAELRLL RLKLKVEQHV ELYQKYSNNS WRYLSNRLLA P SDSPEWLS FDVTGVVRQW LSRGGEIEGF RLSAHCSCDS RDNTLQVDIN GFTTGRRGDL ATIHGMNRPF LLLMATPLER AQ HLQSSRH RR |
-分子 #2: Transforming growth factor beta-1
分子 | 名称: Transforming growth factor beta-1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.809812 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: ALDTNYCFSS TEKNCCVRQL YIDFRKDLGW KWIHEPKGYH ANFCLGPCPY IWSLDTQYSK VLALYNQHNP GASAAPCCVP QALEPLPIV YYVGRKPKVE QLSNMIVRSC KCS |
-分子 #3: Transforming growth factor beta activator LRRC32
分子 | 名称: Transforming growth factor beta activator LRRC32 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 65.358488 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: HQDKVPCKMV DKKVSCQVLG LLQVPSVLPP DTETLDLSGN QLRSILASPL GFYTALRHLD LSTNEISFLQ PGAFQALTHL EHLSLAHNR LAMATALSAG GLGPLPRVTS LDLSGNSLYS GLLERLLGEA PSLHTLSLAE NSLTRLTRHT FRDMPALEQL D LHSNVLMD ...文字列: HQDKVPCKMV DKKVSCQVLG LLQVPSVLPP DTETLDLSGN QLRSILASPL GFYTALRHLD LSTNEISFLQ PGAFQALTHL EHLSLAHNR LAMATALSAG GLGPLPRVTS LDLSGNSLYS GLLERLLGEA PSLHTLSLAE NSLTRLTRHT FRDMPALEQL D LHSNVLMD IEDGAFEGLP RLTHLNLSRN SLTCISDFSL QQLRVLDLSC NSIEAFQTAS QPQAEFQLTW LDLRENKLLH FP DLAALPR LIYLNLSNNL IRLPTGPPQD SKGIHAPSEG WSALPLSAPS GNASGRPLSQ LLNLDLSYNE IELIPDSFLE HLT SLCFLN LSRNCLRTFE ARRLGSLPCL MLLDLSHNAL ETLELGARAL GSLRTLLLQG NALRDLPPYT FANLASLQRL NLQG NRVSP CGGPDEPGPS GCVAFSGITS LRSLSLVDNE IELLRAGAFL HTPLTELDLS SNPGLEVATG ALGGLEASLE VLALQ GNGL MVLQVDLPCF ICLKRLNLAE NRLSHLPAWT QAVSLEVLDL RNNSFSLLPG SAMGGLETSL RRLYLQGNPL SCCGNG WLA AQLHQGRVDV DATQDLICRF SSQEEVSLSH VRPEDCEK |
-分子 #4: 28G11 Fab heavy chain
分子 | 名称: 28G11 Fab heavy chain / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 24.529211 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: EVQLVQPGAE LRNSGASVKV SCKASGYRFT SYYIDWVRQA PGQGLEWMGR IDPEDGGTKY AQKFQGRVTF TADTSTSTAY VELSSLRSE DTAVYYCARN EWETVVVGDL MYEYEYWGQG TQVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN ...文字列: EVQLVQPGAE LRNSGASVKV SCKASGYRFT SYYIDWVRQA PGQGLEWMGR IDPEDGGTKY AQKFQGRVTF TADTSTSTAY VELSSLRSE DTAVYYCARN EWETVVVGDL MYEYEYWGQG TQVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPK |
-分子 #5: 28G11 Fab light chain
分子 | 名称: 28G11 Fab light chain / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 23.091578 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: DIQMTQSPSS LSASLGDRVT ITCQASQSIS SYLAWYQQKP GQAPNILIYG ASRLKTGVPS RFSGSGSGTS FTLTISGLEA EDAGTYYCQ QYASVPVTFG QGTKVELKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...文字列: DIQMTQSPSS LSASLGDRVT ITCQASQSIS SYLAWYQQKP GQAPNILIYG ASRLKTGVPS RFSGSGSGTS FTLTISGLEA EDAGTYYCQ QYASVPVTFG QGTKVELKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 80 % / チャンバー内温度: 4 K / 装置: LEICA EM GP |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy 最大 デフォーカス(公称値): 2.8000000000000003 µm 最小 デフォーカス(公称値): 0.8 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 40.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 418886 |