6FLC

2C8 Fab bound to EDIII of DenV 2

6FLC の概要

• エントリーDOI: 10.2210/pdb6flc/pdb
• 分子名称: Light chain of 2C8 Fab, Heavy chain of 2C8 Fab, Domain III of Dengue virus 2, ... (5 entities in total)
• 機能のキーワード: dengue virus, antibody, macromolecular complex, viral protein
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 119698.24

構造登録者

Flanagan, A.,Renner, M.,Grimes, J.M. (登録日: 2018-01-25, 公開日: 2018-10-24, 最終更新日: 2024-11-13)

主引用文献

Renner, M.,Flanagan, A.,Dejnirattisai, W.,Puttikhunt, C.,Kasinrerk, W.,Supasa, P.,Wongwiwat, W.,Chawansuntati, K.,Duangchinda, T.,Cowper, A.,Midgley, C.M.,Malasit, P.,Huiskonen, J.T.,Mongkolsapaya, J.,Screaton, G.R.,Grimes, J.M.
Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus.
Nat. Immunol., 19:1248-1256, 2018

PubMed Abstract: Dengue virus is a major pathogen, and severe infections can lead to life-threatening dengue hemorrhagic fever. Dengue virus exists as four serotypes, and dengue hemorrhagic fever is often associated with secondary heterologous infections. Antibody-dependent enhancement (ADE) may drive higher viral loads in these secondary infections and is purported to result from antibodies that recognize dengue virus but fail to fully neutralize it. Here we characterize two antibodies, 2C8 and 3H5, that bind to the envelope protein. Antibody 3H5 is highly unusual as it not only is potently neutralizing but also promotes little if any ADE, whereas antibody 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immunocomplexes of 3H5 and dengue virus do not efficiently interact with Fcγ receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided.

PubMed: 30323338
DOI: 10.1038/s41590-018-0227-7

実験手法

X-RAY DIFFRACTION (2 Å)