4JHW

Crystal Structure of Respiratory Syncytial Virus Fusion Glycoprotein Stabilized in the Prefusion Conformation by Human Antibody D25

4JHW の概要

• エントリーDOI: 10.2210/pdb4jhw/pdb
• 関連するPDBエントリー: 4JHA
• 分子名称: D25 antigen-binding fragment heavy chain, D25 light chain, Fusion glycoprotein F0 (3 entities in total)
• 機能のキーワード: immunoglobulin; type i fusion protein, membrane fusion, immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Virion membrane; Single-pass type I membrane protein: P03420
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 102715.94

構造登録者

Mclellan, J.S.,Chen, M.,Leung, S.,Graepel, K.W.,Du, X.,Yang, Y.,Zhou, T.,Baxa, U.,Yasuda, E.,Beaumont, T.,Kumar, A.,Modjarrad, K.,Zheng, Z.,Zhao, M.,Xia, N.,Kwong, P.D.,Graham, B.S. (登録日: 2013-03-05, 公開日: 2013-05-01, 最終更新日: 2024-10-16)

主引用文献

McLellan, J.S.,Chen, M.,Leung, S.,Graepel, K.W.,Du, X.,Yang, Y.,Zhou, T.,Baxa, U.,Yasuda, E.,Beaumont, T.,Kumar, A.,Modjarrad, K.,Zheng, Z.,Zhao, M.,Xia, N.,Kwong, P.D.,Graham, B.S.
Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Science, 340:1113-1117, 2013

PubMed Abstract: The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease.

PubMed: 23618766
DOI: 10.1126/science.1234914

実験手法

X-RAY DIFFRACTION (3.6 Å)