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基本情報
登録情報 | データベース: EMDB / ID: EMD-8427 | |||||||||
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タイトル | Initial contact of HIV-1 Env with CD4: cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145 | |||||||||
![]() | Initial contact of HIV-1 Env with CD4: cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145 | |||||||||
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機能・相同性 | ![]() 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 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 / T cell activation / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of T cell activation / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / MHC class II protein complex binding / Clathrin-mediated endocytosis / virus receptor activity / signaling receptor activity / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / positive regulation of viral entry into host cell / early endosome / 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 / structural molecule activity / positive regulation of DNA-templated transcription / virion membrane / 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 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6.8 Å | |||||||||
![]() | Acharya P / Kwong PD / Potter CS / Carragher B | |||||||||
![]() | ![]() タイトル: Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. 著者: Qingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / ...著者: Qingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / Tongqing Zhou / William J Rice / Christoph Wigge / Bridget Carragher / Clinton S Potter / Peter D Kwong / Paolo Lusso / ![]() 要旨: Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial ...Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 6.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.6 KB 16.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 11.1 KB | 表示 | ![]() |
画像 | ![]() | 59.4 KB | ||
その他 | ![]() | 10.8 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Initial contact of HIV-1 Env with CD4: cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.1 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
-追加マップ: HIV-1 Env with CD4: cryo-EM structure of BG505...
ファイル | emd_8427_additional.map | ||||||||||||
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注釈 | HIV-1 Env with CD4: cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : HIV-1 Env trimer
全体 | 名称: HIV-1 Env trimer |
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要素 |
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-超分子 #1: HIV-1 Env trimer
超分子 | 名称: HIV-1 Env trimer / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: ![]() ![]() |
組換発現 | 生物種: ![]() |
-超分子 #2: HIV-1 Env trimer in complex with antibody PGT145 and CD4
超分子 | 名称: HIV-1 Env trimer in complex with antibody PGT145 and CD4 タイプ: complex / ID: 2 / 親要素: 1 |
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由来(天然) | 生物種: ![]() ![]() |
-超分子 #3: Antibody PGT145
超分子 | 名称: Antibody PGT145 / タイプ: complex / ID: 3 / 親要素: 2 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-超分子 #4: CD4
超分子 | 名称: CD4 / タイプ: complex / ID: 4 / 親要素: 2 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-超分子 #5: HIV-1 trimer
超分子 | 名称: HIV-1 trimer / タイプ: complex / ID: 5 / 親要素: 2 |
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由来(天然) | 生物種: ![]() ![]() |
組換発現 | 生物種: ![]() |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1 mg/mL | ||||||
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緩衝液 | pH: 7.2 構成要素:
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グリッド | 材質: GOLD / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 雰囲気: OTHER | ||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 85 % / チャンバー内温度: 298 K / 装置: GATAN CRYOPLUNGE 3 |
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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) 平均露光時間: 10.0 sec. / 平均電子線量: 8.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 倍率(補正後): 22000 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: RIGID BODY FIT / 当てはまり具合の基準: Correlation Coefficient |
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得られたモデル | ![]() PDB-5u1f: |