+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 3j05 | ||||||
---|---|---|---|---|---|---|---|
タイトル | Three-dimensional structure of Dengue virus serotype 1 complexed with HMAb 14c10 Fab | ||||||
要素 | envelope protein | ||||||
キーワード | VIRUS / flavivirus / dengue / serotype 1 / envelope protein / E protein / mature virus | ||||||
機能・相同性 | 機能・相同性情報 symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / serine-type endopeptidase activity / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / metal ion binding 類似検索 - 分子機能 | ||||||
生物種 | Dengue virus 1 (デング熱ウイルス) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 7 Å | ||||||
データ登録者 | Teoh, E.P. / Kukkaro, P. / Teo, E.W. / Lim, A. / Tan, T.T. / Shi, P.Y. / Yip, A. / Schul, W. / Leo, Y.S. / Chan, S.H. ...Teoh, E.P. / Kukkaro, P. / Teo, E.W. / Lim, A. / Tan, T.T. / Shi, P.Y. / Yip, A. / Schul, W. / Leo, Y.S. / Chan, S.H. / Smith, K.G.C. / Ooi, E.E. / Kemeny, D.M. / Ng, G. / Ng, M.L. / Alonso, S. / Fisher, D. / Hanson, B. / Lok, S.M. / MacAry, P.A. | ||||||
引用 | ジャーナル: Sci Transl Med / 年: 2012 タイトル: The structural basis for serotype-specific neutralization of dengue virus by a human antibody. 著者: Ee Ping Teoh / Petra Kukkaro / En Wei Teo / Angeline P C Lim / Tze Tong Tan / Andy Yip / Wouter Schul / Myint Aung / Victor A Kostyuchenko / Yee Sin Leo / Soh Ha Chan / Kenneth G C Smith / ...著者: Ee Ping Teoh / Petra Kukkaro / En Wei Teo / Angeline P C Lim / Tze Tong Tan / Andy Yip / Wouter Schul / Myint Aung / Victor A Kostyuchenko / Yee Sin Leo / Soh Ha Chan / Kenneth G C Smith / Annie Hoi Yi Chan / Gang Zou / Eng Eong Ooi / D Michael Kemeny / Grace K Tan / Jowin K W Ng / Mah Lee Ng / Sylvie Alonso / Dale Fisher / Pei-Yong Shi / Brendon J Hanson / Shee-Mei Lok / Paul A MacAry / 要旨: Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to ...Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to that serotype but offers only transient protection against the other serotypes. Identification of the protective determinants of the human antibody response to DENV is a vital requirement for the design and evaluation of future preventative therapies and treatments. Here, we describe the isolation of a neutralizing antibody from a DENV1-infected patient. The human antibody 14c10 (HM14c10) binds specifically to DENV1. HM14c10 neutralizes the virus principally by blocking virus attachment; at higher concentrations, a post-attachment step can also be inhibited. In vivo studies show that the HM14c10 antibody has antiviral activity at picomolar concentrations. A 7 Å resolution cryoelectron microscopy map of Fab fragments of HM14c10 in a complex with DENV1 shows targeting of a discontinuous epitope that spans the adjacent surface of envelope protein dimers. As found previously, a human antibody specific for the related West Nile virus binds to a similar quaternary structure, suggesting that this could be an immunodominant epitope. These findings provide a structural and molecular context for durable, serotype-specific immunity to DENV infection. | ||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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 | 3j05.cif.gz | 46.7 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb3j05.ent.gz | 29.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 3j05.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
文書・要旨 | 3j05_validation.pdf.gz | 904.1 KB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 3j05_full_validation.pdf.gz | 906 KB | 表示 | |
XML形式データ | 3j05_validation.xml.gz | 21.8 KB | 表示 | |
CIF形式データ | 3j05_validation.cif.gz | 31.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/j0/3j05 ftp://data.pdbj.org/pub/pdb/validation_reports/j0/3j05 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
| x 60
2 |
|
3 |
| x 5
4 |
| x 6
5 |
|
対称性 | 点対称性: (シェーンフリース記号: I (正20面体型対称)) |
-要素
#1: タンパク質 | 分子量: 43750.883 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Dengue virus 1 (デング熱ウイルス) プラスミド: pMTBip/V5-His / 細胞株 (発現宿主): S2 発現宿主: Drosophila melanogaster (キイロショウジョウバエ) 参照: UniProt: Q689G3 配列の詳細 | THE AUTHORS STATE THAT THERE ARE NO SEQUENCE CONFLICTS BETWEEN THE SEQUENCE IN THE PDB FILE AND ...THE AUTHORS STATE THAT THERE ARE NO SEQUENCE CONFLICTS BETWEEN THE SEQUENCE IN THE PDB FILE AND SEQUENCE DATABASE REFERENCE NCBI BAD42413. | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Dengue virus serotype 1 with Fab fragment of human monoclonal antibody 14c10 タイプ: COMPLEX / 詳細: 120 Fab molecules bind to one dengue virion |
---|---|
ウイルスについての詳細 | 中空か: NO / エンベロープを持つか: YES / ホストのカテゴリ: INVERTERBRATES / 単離: STRAIN / タイプ: VIRION |
天然宿主 | 生物種: Aedes albopictus |
緩衝液 | pH: 8 / 詳細: 120 mM NaCl, 12 mM Tris-HCl, pH 8.0, 1 mM EDTA |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: 120 mM NaCl, 12 mM Tris-HCl, pH 8.0, 1 mM EDTA |
急速凍結 | 装置: FEI VITROBOT MARK I / 凍結剤: ETHANE / 湿度: 100 % / 手法: 1 second blotting |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS / 日付: 2010年9月27日 |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 47000 X / 最大 デフォーカス(公称値): 4900 nm / 最小 デフォーカス(公称値): 760 nm / Cs: 2.7 mm / カメラ長: 0 mm |
試料ホルダ | 試料ホルダーモデル: OTHER / 資料ホルダタイプ: Titan krios cryoholder / 温度: 100 K / 傾斜角・最大: 0 ° / 傾斜角・最小: 0 ° |
撮影 | 電子線照射量: 16 e/Å2 / フィルム・検出器のモデル: GENERIC GATAN |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 相対比: 1 |
-解析
EMソフトウェア |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | 詳細: each particle | ||||||||||||
対称性 | 点対称性: I (正20面体型対称) | ||||||||||||
3次元再構成 | 手法: Cross-common lines / 解像度: 7 Å / 解像度の算出法: FSC 0.5 CUT-OFF / 粒子像の数: 2129 / ピクセルサイズ(公称値): 1.9 Å / ピクセルサイズ(実測値): 1.9 Å / 詳細: particles were selected manually / 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 / Target criteria: correlation 詳細: REFINEMENT PROTOCOL--rigid body DETAILS--The domains were fitted separately using Fit In Map feature in Chimera | ||||||||||||
原子モデル構築 | PDB-ID: 3G7T Accession code: 3G7T / Source name: PDB / タイプ: experimental model | ||||||||||||
精密化ステップ | サイクル: LAST
|