+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0502 | |||||||||||||||||||||
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タイトル | Cryo-EM structure of full-length human STING in the apo state | |||||||||||||||||||||
マップデータ | Full-length human STING in the apo state | |||||||||||||||||||||
試料 |
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キーワード | ER / membrane / adaptor / IMMUNE SYSTEM | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 STING complex / STING mediated induction of host immune responses / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / proton channel activity / 2',3'-cyclic GMP-AMP binding / pattern recognition receptor signaling pathway / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN ...STING complex / STING mediated induction of host immune responses / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / proton channel activity / 2',3'-cyclic GMP-AMP binding / pattern recognition receptor signaling pathway / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN / cyclic-di-GMP binding / positive regulation of type I interferon-mediated signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / reticulophagy / cellular response to exogenous dsRNA / cellular response to organic cyclic compound / positive regulation of type I interferon production / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / cellular response to interferon-beta / positive regulation of defense response to virus by host / signaling adaptor activity / activation of innate immune response / antiviral innate immune response / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of interferon-beta production / autophagosome / protein complex oligomerization / Regulation of innate immune responses to cytosolic DNA / secretory granule membrane / positive regulation of DNA-binding transcription factor activity / cytoplasmic vesicle membrane / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / peroxisome / monoatomic ion transmembrane transport / regulation of inflammatory response / cytoplasmic vesicle / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / plasma membrane / cytosol 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: 4.1 Å | |||||||||||||||||||||
データ登録者 | Shang G / Zhang C | |||||||||||||||||||||
資金援助 | 米国, 6件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. 著者: Guijun Shang / Conggang Zhang / Zhijian J Chen / Xiao-Chen Bai / Xuewu Zhang / 要旨: Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds ...Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain. The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP. However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180° rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses. | |||||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0502.map.gz | 32.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0502-v30.xml emd-0502.xml | 12 KB 12 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_0502_fsc.xml | 7.6 KB | 表示 | FSCデータファイル |
画像 | emd_0502.png | 147.6 KB | ||
Filedesc metadata | emd-0502.cif.gz | 5.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0502 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0502 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0502_validation.pdf.gz | 510.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0502_full_validation.pdf.gz | 510.5 KB | 表示 | |
XML形式データ | emd_0502_validation.xml.gz | 9.8 KB | 表示 | |
CIF形式データ | emd_0502_validation.cif.gz | 12.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0502 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0502 | HTTPS FTP |
-関連構造データ
-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_0502.map.gz / 形式: CCP4 / 大きさ: 35.3 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Full-length human STING in the apo state | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : full-length human STING
全体 | 名称: full-length human STING |
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要素 |
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-超分子 #1: full-length human STING
超分子 | 名称: full-length human STING / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Stimulator of interferon protein
分子 | 名称: Stimulator of interferon protein / 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: 42.985379 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MPHSSLHPSI PCPRGHGAQK AALVLLSACL VTLWGLGEPP EHTLRYLVLH LASLQLGLLL NGVCSLAEEL RHIHSRYRGS YWRTVRACL GCPLRRGALL LLSIYFYYSL PNAVGPPFTW MLALLGLSQA LNILLGLKGL APAEISAVCE KGNFNVAHGL A WSYYIGYL ...文字列: MPHSSLHPSI PCPRGHGAQK AALVLLSACL VTLWGLGEPP EHTLRYLVLH LASLQLGLLL NGVCSLAEEL RHIHSRYRGS YWRTVRACL GCPLRRGALL LLSIYFYYSL PNAVGPPFTW MLALLGLSQA LNILLGLKGL APAEISAVCE KGNFNVAHGL A WSYYIGYL RLILPELQAR IRTYNQHYNN LLRGAVSQRL YILLPLDCGV PDNLSMADPN IRFLDKLPQQ TGDRAGIKDR VY SNSIYEL LENGQRAGTC VLEYATPLQT LFAMSQYSQA GFSREDRLEQ AKLFCRTLED ILADAPESQN NCRLIAYQEP ADD SSFSLS QEVLRHLRQE EKEEVTVGSL KTSAVPSTST MSQEPELLIS GMEKPLPLRT DFSLEVLFQ UniProtKB: Stimulator of interferon genes protein |
-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
濃度 | 4.5 mg/mL |
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緩衝液 | pH: 8 |
グリッド | 前処理 - タイプ: GLOW DISCHARGE / 詳細: unspecified |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS / エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 50.0 e/Å2 |
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 FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: AB INITIO MODEL |
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得られたモデル | PDB-6nt5: |