+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8407 | ||||||||||||
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タイトル | Cryo-EM structure of a BG505 Env-sCD4-17b-8ANC195 complex | ||||||||||||
マップデータ | BG505 SOSIP in complex with sCD4, 17b Fab, and 8ANC195 Fab. | ||||||||||||
試料 |
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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 / T cell differentiation / Generation of second messenger molecules / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / T cell activation / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / positive regulation of T cell activation / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / MHC class II protein complex binding / Clathrin-mediated endocytosis / signaling receptor activity / virus receptor activity / clathrin-dependent endocytosis of virus by host cell / defense response to Gram-negative bacterium / positive regulation of canonical NF-kappaB signal transduction / adaptive immune response / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / early endosome / positive regulation of viral entry into host cell / cell surface receptor signaling pathway / viral protein processing / cell adhesion / immune response / positive regulation of protein phosphorylation / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / virion attachment to host cell / apoptotic process / protein kinase binding / host cell plasma membrane / positive regulation of DNA-templated transcription / virion membrane / structural molecule activity / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 8.9 Å | ||||||||||||
データ登録者 | Wang H / Bjorkman PJ | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2016 タイトル: Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop. 著者: Haoqing Wang / Alexander A Cohen / Rachel P Galimidi / Harry B Gristick / Grant J Jensen / Pamela J Bjorkman / 要旨: The HIV-1 envelope (Env) glycoprotein, a trimer of gp120-gp41 heterodimers, relies on conformational flexibility to function in fusing the viral and host membranes. Fusion is achieved after gp120 ...The HIV-1 envelope (Env) glycoprotein, a trimer of gp120-gp41 heterodimers, relies on conformational flexibility to function in fusing the viral and host membranes. Fusion is achieved after gp120 binds to CD4, the HIV-1 receptor, and a coreceptor, capturing an open conformational state in which the fusion machinery on gp41 gains access to the target cell membrane. In the well-characterized closed Env conformation, the gp120 V1V2 loops interact at the apex of the Env trimer. Less is known about the structure of the open CD4-bound state, in which the V1V2 loops must rearrange and separate to allow access to the coreceptor binding site. We identified two anti-HIV-1 antibodies, the coreceptor mimicking antibody 17b and the gp120-gp41 interface-spanning antibody 8ANC195, that can be added as Fabs to a soluble native-like Env trimer to stabilize it in a CD4-bound conformation. Here, we present an 8.9-Å cryo-electron microscopy structure of a BG505 Env-sCD4-17b-8ANC195 complex, which reveals large structural rearrangements in gp120, but small changes in gp41, compared with closed Env structures. The gp120 protomers are rotated and separated in the CD4-bound structure, and the three V1V2 loops are displaced by ∼40 Å from their positions at the trimer apex in closed Env to the sides of the trimer in positions adjacent to, and interacting with, the three bound CD4s. These results are relevant to understanding CD4-induced conformational changes leading to coreceptor binding and fusion, and HIV-1 Env conformational dynamics, and describe a target structure relevant to drug design and vaccine efforts. | ||||||||||||
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_8407.map.gz | 203.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8407-v30.xml emd-8407.xml | 22.5 KB 22.5 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_8407_fsc.xml | 13.4 KB | 表示 | FSCデータファイル |
画像 | emd_8407.png | 238.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8407 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8407 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_8407_validation.pdf.gz | 475.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_8407_full_validation.pdf.gz | 475.4 KB | 表示 | |
XML形式データ | emd_8407_validation.xml.gz | 13.7 KB | 表示 | |
CIF形式データ | emd_8407_validation.cif.gz | 18.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8407 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8407 | 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_8407.map.gz / 形式: CCP4 / 大きさ: 226.3 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | BG505 SOSIP in complex with sCD4, 17b Fab, and 8ANC195 Fab. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.82 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 : BG505 SOSIP-sCD4-17b-8ANC195 complex
+超分子 #1: BG505 SOSIP-sCD4-17b-8ANC195 complex
+超分子 #3: 17b Fab
+超分子 #4: BG505 SOSIP trimer
+超分子 #5: 8ANC195 G52K5 Fab
+超分子 #2: CD4 D1-D2 domain
+分子 #1: BG505 SOSIP gp41
+分子 #2: BG505 SOSIP gp120
+分子 #3: T-cell surface glycoprotein CD4
+分子 #4: 17b Fab VL domain
+分子 #5: 17b Fab VH domain
+分子 #6: 8ANC195 G52K5 VH domain
+分子 #7: 8ANC195 G52K5 VL domain
-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: 8 |
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凍結 | 凍結剤: ETHANE-PROPANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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 / 平均露光時間: 3.5 sec. / 平均電子線量: 35.0 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 / Cs: 2.7 mm |
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
詳細 | phenix_real.space.refine |
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精密化 | プロトコル: RIGID BODY FIT |
得られたモデル | PDB-5thr: |