ジャーナル: J Virol / 年: 2014 タイトル: Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies. 著者: Jason Porta / Joyce Jose / John T Roehrig / Carol D Blair / Richard J Kuhn / Michael G Rossmann / 要旨: Alphaviruses are serious, sometimes lethal human pathogens that belong to the family Togaviridae. The structures of human Venezuelan equine encephalitis virus (VEEV), an alphavirus, in complex with ...Alphaviruses are serious, sometimes lethal human pathogens that belong to the family Togaviridae. The structures of human Venezuelan equine encephalitis virus (VEEV), an alphavirus, in complex with two strongly neutralizing antibody Fab fragments (F5 and 3B4C-4) have been determined using a combination of cryo-electron microscopy and homology modeling. We characterize these monoclonal antibody Fab fragments, which are known to abrogate VEEV infectivity by binding to the E2 (envelope) surface glycoprotein. Both of these antibody Fab fragments cross-link the surface E2 glycoproteins and therefore probably inhibit infectivity by blocking the conformational changes that are required for making the virus fusogenic. The F5 Fab fragment cross-links E2 proteins within one trimeric spike, whereas the 3B4C-4 Fab fragment cross-links E2 proteins from neighboring spikes. Furthermore, F5 probably blocks the receptor-binding site, whereas 3B4C-4 sterically hinders the exposure of the fusion loop at the end of the E2 B-domain. IMPORTANCE: Alphaviral infections are transmitted mainly by mosquitoes. Venezuelan equine encephalitis virus (VEEV) is an alphavirus with a wide distribution across the globe. No effective vaccines ...IMPORTANCE: Alphaviral infections are transmitted mainly by mosquitoes. Venezuelan equine encephalitis virus (VEEV) is an alphavirus with a wide distribution across the globe. No effective vaccines exist for alphaviral infections. Therefore, a better understanding of VEEV and its associated neutralizing antibodies will help with the development of effective drugs and vaccines.
履歴
登録
2014年6月5日
登録サイト: PDBE / 処理サイト: PDBE
改定 1.0
2014年10月15日
Provider: repository / タイプ: Initial release
改定 1.1
2017年8月23日
Group: Data collection / カテゴリ: em_software / Item: _em_software.image_processing_id
モード: BRIGHT FIELD / 倍率(公称値): 59000 X / 倍率(補正後): 60521 X / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1500 nm / Cs: 2.7 mm
試料ホルダ
温度: 100 K
撮影
電子線照射量: 24 e/Å2 / フィルム・検出器のモデル: KODAK SO-163 FILM
画像スキャン
デジタル画像の数: 112
放射波長
相対比: 1
-
解析
EMソフトウェア
ID
名称
バージョン
カテゴリ
1
EMAN
1
3次元再構成
2
EMAN
2
3次元再構成
CTF補正
詳細: EACH IMAGE
対称性
点対称性: I (正20面体型対称)
3次元再構成
手法: COMMON LINES / 解像度: 17 Å / 粒子像の数: 1389 / ピクセルサイズ(公称値): 1.07 Å / ピクセルサイズ(実測値): 1.11 Å 詳細: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-2645. (DEPOSITION ID: 12481). 対称性のタイプ: POINT
原子モデル構築
プロトコル: OTHER / 空間: REAL / 詳細: REFINEMENT PROTOCOL--HOMOLOGY