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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 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX / VIRUS | ||||||
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 / T cell receptor complex / extracellular matrix structural constituent / 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 / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / T cell activation / 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 / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / positive regulation of T cell activation / 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 viral entry into host cell / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / early endosome / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / immune response / membrane raft / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / external side of plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / virion attachment to host cell / endoplasmic reticulum membrane / protein kinase binding / host cell plasma membrane / structural molecule activity / virion membrane / positive regulation of DNA-templated transcription / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() | ||||||
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 | ||||||
![]() | Scharf, L. / Wang, H. / Gao, H. / Chen, S. / McDowall, A. / Bjorkman, P. | ||||||
![]() | ![]() 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 |
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 806.4 KB | 表示 | ![]() |
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PDB形式 | ![]() | 648.1 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 814.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 149.4 KB | 表示 | |
CIF形式データ | ![]() | 218.5 KB | 表示 | |
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
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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) ![]() ![]() プラスミド: PTT5 / 細胞株 (発現宿主): HEK-6E / 発現宿主: ![]() #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) ![]() ![]() |
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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) ![]() ![]() #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) ![]() ![]() #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) ![]() ![]() #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) ![]() ![]() |
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-糖 , 1種, 45分子 ![](data/chem/img/NAG.gif)
#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 |
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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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 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 |
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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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