5K6C

Crystal structure of prefusion-stabilized RSV F single-chain 9-10 DS-Cav1 variant.

5K6C の概要

• エントリーDOI: 10.2210/pdb5k6c/pdb
• 関連するPDBエントリー: 5K6B 5K6F 5K6G 5K6H 5K6I
• 分子名称: Fusion glycoprotein F0,Fusion glycoprotein F0, SULFATE ION (2 entities in total)
• 機能のキーワード: respiratory syncytial virus, prefusion, vaccine, stabilized, viral protein
• 由来する生物種: Human respiratory syncytial virus A (strain A2); 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: 1
• 化学式量合計: 49341.19

構造登録者

Joyce, M.G.,Zhang, B.,Lai, Y.T.,Mascola, J.R.,Kwong, P.D. (登録日: 2016-05-24, 公開日: 2016-10-12, 最終更新日: 2024-11-13)

主引用文献

Joyce, M.G.,Zhang, B.,Ou, L.,Chen, M.,Chuang, G.Y.,Druz, A.,Kong, W.P.,Lai, Y.T.,Rundlet, E.J.,Tsybovsky, Y.,Yang, Y.,Georgiev, I.S.,Guttman, M.,Lees, C.R.,Pancera, M.,Sastry, M.,Soto, C.,Stewart-Jones, G.B.,Thomas, P.V.,Van Galen, J.G.,Baxa, U.,Lee, K.K.,Mascola, J.R.,Graham, B.S.,Kwong, P.D.
Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV.
Nat.Struct.Mol.Biol., 23:811-820, 2016

PubMed Abstract: Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.

PubMed: 27478931
DOI: 10.1038/nsmb.3267

実験手法

X-RAY DIFFRACTION (3.576 Å)