3UAJ

Crystal structure of the envelope glycoprotein ectodomain from dengue virus serotype 4 in complex with the fab fragment of the chimpanzee monoclonal antibody 5H2

3UAJ の概要

• エントリーDOI: 10.2210/pdb3uaj/pdb
• 関連するPDBエントリー: 3UC0
• 分子名称: envelope protein, Heavy chain, monoclonal antibody 5H2, Light chain, monoclonal antibody 5H2, ... (4 entities in total)
• 機能のキーワード: dengue antibody membrane fusion, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Dengue virus 4; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 192139.46

構造登録者

Cockburn, J.J.B.,Stura, E.A.,Navarro-Sanchez, M.E.,Rey, F.A. (登録日: 2011-10-21, 公開日: 2011-12-14, 最終更新日: 2024-10-30)

主引用文献

Cockburn, J.J.,Navarro Sanchez, M.E.,Goncalvez, A.P.,Zaitseva, E.,Stura, E.A.,Kikuti, C.M.,Duquerroy, S.,Dussart, P.,Chernomordik, L.V.,Lai, C.J.,Rey, F.A.
Structural insights into the neutralization mechanism of a higher primate antibody against dengue virus.
Embo J., 31:767-779, 2012

PubMed Abstract: The four serotypes of dengue virus (DENV-1 to -4) cause the most important emerging viral disease. Protein E, the principal viral envelope glycoprotein, mediates fusion of the viral and endosomal membranes during virus entry and is the target of neutralizing antibodies. However, the epitopes of strongly neutralizing human antibodies have not been described despite their importance to vaccine development. The chimpanzee Mab 5H2 potently neutralizes DENV-4 by binding to domain I of E. The crystal structure of Fab 5H2 bound to E from DENV-4 shows that antibody binding prevents formation of the fusogenic hairpin conformation of E, which together with in-vitro assays, demonstrates that 5H2 neutralizes by blocking membrane fusion in the endosome. Furthermore, we show that human sera from patients recovering from DENV-4 infection contain antibodies that bind to the 5H2 epitope region on domain I. This study, thus, provides new information and tools for effective vaccine design to prevent dengue disease.

PubMed: 22139356
DOI: 10.1038/emboj.2011.439

実験手法

X-RAY DIFFRACTION (3.232 Å)