+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5a8h | ||||||
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タイトル | cryo-ET subtomogram averaging of BG505 SOSIP.664 in complex with sCD4, 17b, and 8ANC195 | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX (ウイルス性) / VIRUS (ウイルス) | ||||||
機能・相同性 | 機能・相同性情報 helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / regulation of T cell activation / extracellular matrix structural constituent / T cell receptor complex / Other interleukin signaling / enzyme-linked receptor protein signaling pathway / Dectin-2 family / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / regulation of calcium ion transport / macrophage differentiation / Generation of second messenger molecules / T cell differentiation / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of calcium-mediated signaling / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / T細胞 / positive regulation of interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / cell surface receptor protein tyrosine kinase signaling pathway / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of T cell activation / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / virus receptor activity / MHC class II protein complex binding / Clathrin-mediated endocytosis / signaling receptor activity / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / 獲得免疫系 / defense response to Gram-negative bacterium / positive regulation of MAPK cascade / positive regulation of viral entry into host cell / エンドソーム / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / viral protein processing / 細胞接着 / 免疫応答 / 脂質ラフト / positive regulation of protein phosphorylation / fusion of virus membrane with host plasma membrane / external side of plasma membrane / virus-mediated perturbation of host defense response / 小胞体 / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / lipid binding / endoplasmic reticulum membrane / virion attachment to host cell / protein kinase binding / host cell plasma membrane / virion membrane / structural molecule activity / positive regulation of DNA-templated transcription / enzyme binding / シグナル伝達 / protein homodimerization activity / zinc ion binding / 生体膜 / identical protein binding / 細胞膜 類似検索 - 分子機能 | ||||||
生物種 | HUMAN IMMUNODEFICIENCY VIRUS 1 (ヒト免疫不全ウイルス) HOMO SAPIENS (ヒト) | ||||||
手法 | 電子顕微鏡法 / 電子線トモグラフィー法 / クライオ電子顕微鏡法 / 解像度: 23 Å | ||||||
データ登録者 | Scharf, L. / Wang, H. / Gao, H. / Chen, S. / McDowall, A. / Bjorkman, P. | ||||||
引用 | ジャーナル: Cell / 年: 2015 タイトル: Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. 著者: Louise Scharf / Haoqing Wang / Han Gao / Songye Chen / Alasdair W McDowall / Pamela J Bjorkman / 要旨: The HIV-1 envelope (Env) spike contains limited epitopes for broadly neutralizing antibodies (bNAbs); thus, most neutralizing antibodies are strain specific. The 8ANC195 epitope, defined by crystal ...The HIV-1 envelope (Env) spike contains limited epitopes for broadly neutralizing antibodies (bNAbs); thus, most neutralizing antibodies are strain specific. The 8ANC195 epitope, defined by crystal and electron microscopy (EM) structures of bNAb 8ANC195 complexed with monomeric gp120 and trimeric Env, respectively, spans the gp120 and gp41 Env subunits. To investigate 8ANC195's gp41 epitope at higher resolution, we solved a 3.58 Å crystal structure of 8ANC195 complexed with fully glycosylated Env trimer, revealing 8ANC195 insertion into a glycan shield gap to contact gp120 and gp41 glycans and protein residues. To determine whether 8ANC195 recognizes the CD4-bound open Env conformation that leads to co-receptor binding and fusion, one of several known conformations of virion-associated Env, we solved EM structures of an Env/CD4/CD4-induced antibody/8ANC195 complex. 8ANC195 binding partially closed the CD4-bound trimer, confirming structural plasticity of Env by revealing a previously unseen conformation. 8ANC195's ability to bind different Env conformations suggests advantages for potential therapeutic applications. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5a8h.cif.gz | 806.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5a8h.ent.gz | 648.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5a8h.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/a8/5a8h ftp://data.pdbj.org/pub/pdb/validation_reports/a8/5a8h | 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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-要素
-タンパク質 , 2種, 6分子 AGMBHN
#1: タンパク質 | 分子量: 34838.691 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) HUMAN IMMUNODEFICIENCY VIRUS 1 (ヒト免疫不全ウイルス) プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) / 参照: UniProt: P35961*PLUS #2: タンパク質 | 分子量: 20503.260 Da / 分子数: 3 / Fragment: SOLUBLE CD4 D1-D2 DOMAINS, RESIDUES26-208 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) / 参照: UniProt: P01730 |
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-抗体 , 4種, 12分子 CIODJPEKQFLR
#3: 抗体 | 分子量: 23399.898 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) #4: 抗体 | 分子量: 24457.387 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) #5: 抗体 | 分子量: 23401.984 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) #6: 抗体 | 分子量: 26125.270 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: HOMO SAPIENS (ヒト) |
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-糖 , 1種, 45分子
#7: 糖 | ChemComp-NAG / |
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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: 電子線トモグラフィー法 |
-試料調製
構成要素 | 名称: SOLUBLE HIV-1 ENV TRIMER BG505 SOSIP.664 IN COMPLEX WITH SOLUBLE CD4S (D1-D2), BROADLY NEUTRALIZING ANTIBODY 17B FABS, AND BROADLY NEUTRALIZING ANTIBODY 8ANC195 VARIANT G32K5 FABS タイプ: COMPLEX |
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緩衝液 | 名称: 20MM TRIS, 50MM NACL / pH: 8 / 詳細: 20MM TRIS, 50MM NACL |
試料 | 濃度: 0.06 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: HOLEY CARBON |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE-PROPANE 詳細: VITRIFICATION 1 -- CRYOGEN- ETHANE-PROPANE MIXTURE, HUMIDITY- 95, TEMPERATURE- 70, INSTRUMENT- FEI |
-電子顕微鏡撮影
実験機器 | モデル: Tecnai F30 / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI F30 / 日付: 2015年1月25日 |
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 FIELDBright-field microscopy / 倍率(公称値): 41000 X / Cs: 2.2 mm |
試料ホルダ | 傾斜角・最大: 60 ° / 傾斜角・最小: -60 ° |
撮影 | 電子線照射量: 120 e/Å2 / フィルム・検出器のモデル: GATAN K2 (4k x 4k) |
画像スキャン | デジタル画像の数: 25 |
放射波長 | 相対比: 1 |
-解析
EMソフトウェア |
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CTF補正 | 詳細: EACH MICROGRAPH | ||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||
3次元再構成 | 手法: SUBTOMOGRAM AVERAGING / 解像度: 23 Å / 粒子像の数: 1745 / ピクセルサイズ(実測値): 2.6 Å 詳細: SUBTOMOGRAM AVERAGING SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3096. (DEPOSITION ID: 13596). 対称性のタイプ: POINT | ||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL / 詳細: METHOD--RIGID BODY | ||||||||||||||||||||
原子モデル構築 | PDB-ID: 1RZK | ||||||||||||||||||||
精密化 | 最高解像度: 23 Å | ||||||||||||||||||||
精密化ステップ | サイクル: LAST / 最高解像度: 23 Å
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