3J6U

Cryo-EM structure of Dengue virus serotype 3 in complex with human antibody 5J7 Fab

3J6U の概要

• エントリーDOI: 10.2210/pdb3j6u/pdb
• 関連するPDBエントリー: 3J6S 3J6T
• EMDBエントリー: 5933 5934 5935
• 分子名称: envelope protein, membrane protein, Fab 5J7 heavy chain, ... (4 entities in total)
• 機能のキーワード: dengue virus, human antibody, neutralization, virus-immune system complex, virus/immune system
• 由来する生物種: Dengue virus 3; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 213818.92

構造登録者

Fibriansah, G.,Tan, J.L.,Smith, S.A.,de Alwis, R.,Ng, T.-S.,Kostyuchenko, V.A.,Kukkaro, P.,de Silva, A.M.,Crowe Jr., J.E.,Lok, S.-M. (登録日: 2014-03-26, 公開日: 2015-03-04, 最終更新日: 2024-02-21)

主引用文献

Fibriansah, G.,Tan, J.L.,Smith, S.A.,de Alwis, R.,Ng, T.S.,Kostyuchenko, V.A.,Jadi, R.S.,Kukkaro, P.,de Silva, A.M.,Crowe, J.E.,Lok, S.M.
A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins.
Nat Commun, 6:6341-6341, 2015

PubMed Abstract: Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 Å resolution cryo-electron microscopy structure of the Fab 5J7-DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody.

PubMed: 25698059
DOI: 10.1038/ncomms7341

実験手法

ELECTRON MICROSCOPY (9 Å)