4MMR

Crystal Structure of Prefusion-stabilized RSV F Variant Cav1 at pH 9.5

4MMR の概要

• エントリーDOI: 10.2210/pdb4mmr/pdb
• 関連するPDBエントリー: 4JHW 4MMQ 4MMS 4MMT 4MMU 4MMV
• 分子名称: Fusion glycoprotein F2, Fusion glycoprotein F1 fused with Fibritin trimerization domain (2 entities in total)
• 機能のキーワード: fusion, membrane, viral protein
• 由来する生物種: Human respiratory syncytial virus A2; 詳細
• 細胞内の位置: Virion membrane; Single-pass type I membrane protein: P03420; Virion : P10104
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54792.43

構造登録者

Stewart-Jones, G.B.E.,McLellan, J.S.,Joyce, M.G.,Sastry, M.,Yang, Y.,Graham, B.S.,Kwong, P.D. (登録日: 2013-09-09, 公開日: 2013-11-20, 最終更新日: 2021-06-02)

主引用文献

McLellan, J.S.,Chen, M.,Joyce, M.G.,Sastry, M.,Stewart-Jones, G.B.,Yang, Y.,Zhang, B.,Chen, L.,Srivatsan, S.,Zheng, A.,Zhou, T.,Graepel, K.W.,Kumar, A.,Moin, S.,Boyington, J.C.,Chuang, G.Y.,Soto, C.,Baxa, U.,Bakker, A.Q.,Spits, H.,Beaumont, T.,Zheng, Z.,Xia, N.,Ko, S.Y.,Todd, J.P.,Rao, S.,Graham, B.S.,Kwong, P.D.
Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.
Science, 342:592-598, 2013

PubMed Abstract: Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site Ø when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site Ø-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.

PubMed: 24179220
DOI: 10.1126/science.1243283

実験手法

X-RAY DIFFRACTION (3.1 Å)