+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6543 | |||||||||
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タイトル | Structure of Simian Immunodeficiency Virus Envelope Spikes bound with CD4 and Monoclonal Antibody 36D5 | |||||||||
マップデータ | Reconstruction of open state SIV envelope spike bound with CD4 and 36D5 | |||||||||
試料 |
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キーワード | Cryoelectron tomography / image processing (デジタル画像処理) / electron microscopy (電子顕微鏡) / immunology (免疫学) / AIDS (後天性免疫不全症候群) / HIV (ヒト免疫不全ウイルス) | |||||||||
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 / 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 / T細胞 / positive regulation of interleukin-2 production / protein tyrosine kinase binding / 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 / 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 / 細胞接着 / 免疫応答 / 脂質ラフト / positive regulation of protein phosphorylation / external side of plasma membrane / 小胞体 / エンベロープ (ウイルス) / lipid binding / endoplasmic reticulum membrane / protein kinase binding / positive regulation of DNA-templated transcription / enzyme binding / シグナル伝達 / protein homodimerization activity / zinc ion binding / identical protein binding / 細胞膜 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) / Simian immunodeficiency virus (サル免疫不全ウイルス) | |||||||||
手法 | サブトモグラム平均法 / クライオ電子顕微鏡法 | |||||||||
データ登録者 | Hu G / Liu J / Roux KH / Taylor KA | |||||||||
引用 | ジャーナル: J Virol / 年: 2017 タイトル: Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5. 著者: Guiqing Hu / Jun Liu / Kenneth H Roux / Kenneth A Taylor / 要旨: The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer ...The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the rapid freezing step, which were separated using statistical analysis. Our results show that the CD4-induced conformational dynamics of the spike enhances binding of the antibody. | |||||||||
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_6543.map.gz | 304.7 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-6543-v30.xml emd-6543.xml | 9.6 KB 9.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_6543.tif | 70.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6543 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6543 | 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_6543.map.gz / 形式: CCP4 / 大きさ: 348.6 KB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Reconstruction of open state SIV envelope spike bound with CD4 and 36D5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 5.7 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 : SIV envelope spike bound to CD4 and monoclonal antibody 36d5 in o...
全体 | 名称: SIV envelope spike bound to CD4 and monoclonal antibody 36d5 in open state |
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要素 |
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-超分子 #1000: SIV envelope spike bound to CD4 and monoclonal antibody 36d5 in o...
超分子 | 名称: SIV envelope spike bound to CD4 and monoclonal antibody 36d5 in open state タイプ: sample / ID: 1000 集合状態: gp120 trimer bound to CD4 and 36D5 in open state Number unique components: 3 |
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-超分子 #1: Simian immunodeficiency virus
超分子 | 名称: Simian immunodeficiency virus / タイプ: virus / ID: 1 / Name.synonym: SIV / NCBI-ID: 11723 / 生物種: Simian immunodeficiency virus / Sci species strain: SIV239/251tail/Supt-CCR5 CL.30 / データベース: NCBI / ウイルスタイプ: VIRION / ウイルス・単離状態: STRAIN / ウイルス・エンベロープ: Yes / ウイルス・中空状態: No / Syn species name: SIV |
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宿主 | 生物種: Cercopithecidae (オナガザル科) / 別称: VERTEBRATES |
-分子 #1: T-cell surface glycoprotein CD4
分子 | 名称: T-cell surface glycoprotein CD4 / タイプ: protein_or_peptide / ID: 1 / Name.synonym: CD4 / 組換発現: No / データベース: NCBI |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 別称: human |
-分子 #2: monoclonal antibody 36D5
分子 | 名称: monoclonal antibody 36D5 / タイプ: protein_or_peptide / ID: 2 / 組換発現: No / データベース: NCBI |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) / 別称: mouse |
-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 | サブトモグラム平均法 |
試料の集合状態 | particle |
-試料調製
凍結 | 凍結剤: ETHANE / 装置: HOMEMADE PLUNGER |
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-電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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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): 5.0 µm / 最小 デフォーカス(公称値): 4.0 µm / 倍率(公称値): 31000 |
試料ステージ | 試料ホルダー: cryo holder / 試料ホルダーモデル: OTHER / Tilt series - Axis1 - Min angle: -65 ° / Tilt series - Axis1 - Max angle: 65 ° |
日付 | 2008年8月16日 |
撮影 | カテゴリ: CCD フィルム・検出器のモデル: TVIPS TEMCAM-F415 (4k x 4k) 平均電子線量: 100 e/Å2 |
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
-画像解析
最終 再構成 | ソフトウェア - 名称: I3, protomo / 使用したサブトモグラム数: 1796 |
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