4UIF

Cryo-EM structure of Dengue virus serotype 2 in complex with antigen-binding fragments of human antibody 2D22

4UIF の概要

• エントリーDOI: 10.2210/pdb4uif/pdb
• 関連するPDBエントリー: 4UIH
• EMDBエントリー: 2967
• 分子名称: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN, DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN, ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN, ... (4 entities in total)
• 機能のキーワード: viral protein, dengue virus, human antibody, cryo-em, neutralization
• 由来する生物種: DENGUE VIRUS 2; 詳細
• 細胞内の位置: Host endoplasmic reticulum membrane ; Multi-pass membrane protein : D6MQ38; Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Lumenal side : E0WXJ3
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 264791.42

構造登録者

Fibriansah, G.,Ibarra, K.D.,Ng, T.-S.,Smith, S.A.,Tan, J.L.,Lim, X.-N.,Ooi, J.S.G.,Kostyuchenko, V.A.,Wang, J.,de Silva, A.M.,Harris, E.,Crowe Junior, J.E.,Lok, S.-M. (登録日: 2015-03-30, 公開日: 2015-07-15, 最終更新日: 2024-05-08)

主引用文献

Fibriansah, G.,Ibarra, K.D.,Ng, T.S.,Smith, S.A.,Tan, J.L.,Lim, X.N.,Ooi, J.S.,Kostyuchenko, V.A.,Wang, J.,de Silva, A.M.,Harris, E.,Crowe, J.E.,Lok, S.M.
Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
Science, 349:88-91, 2015

PubMed Abstract: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.

PubMed: 26138979
DOI: 10.1126/science.aaa8651

実験手法

ELECTRON MICROSCOPY (6.5 Å)