5N0A

Crystal structure of A259C covalently linked dengue 2 virus envelope glycoprotein dimer in complex with the Fab fragment of the broadly neutralizing human antibody EDE2 A11

5N0A の概要

• エントリーDOI: 10.2210/pdb5n0a/pdb
• 分子名称: Envelope Glycoprotein E, BROADLY NEUTRALIZING HUMAN ANTIBODY EDE2 A11 HEAVY CHAIN, BROADLY NEUTRALIZING HUMAN ANTIBODY EDE2 A11, ... (4 entities in total)
• 機能のキーワード: immune system-viral protein complex, dengue virus, envelope fusion protein, broadly neutralizing antibody, immune system/viral protein
• 由来する生物種: Dengue virus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 203994.64

構造登録者

Vaney, M.C.,Rouvinski, A.,Guardado-Calvo, P.,Sharma, A.,Rey, F.A. (登録日: 2017-02-02, 公開日: 2017-06-07, 最終更新日: 2024-11-06)

主引用文献

Rouvinski, A.,Dejnirattisai, W.,Guardado-Calvo, P.,Vaney, M.C.,Sharma, A.,Duquerroy, S.,Supasa, P.,Wongwiwat, W.,Haouz, A.,Barba-Spaeth, G.,Mongkolsapaya, J.,Rey, F.A.,Screaton, G.R.
Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope.
Nat Commun, 8:15411-15411, 2017

PubMed Abstract: A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine.

PubMed: 28534525
DOI: 10.1038/ncomms15411

実験手法

X-RAY DIFFRACTION (3.9 Å)