5W23

Crystal Structure of RSV F in complex with 5C4 Fab

5W23 の概要

• エントリーDOI: 10.2210/pdb5w23/pdb
• 分子名称: Fusion glycoprotein F0, 5C4 Fab heavy chain, 5C4 Fab light chain, ... (4 entities in total)
• 機能のキーワード: rsv, complex, fab, antibody, neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human respiratory syncytial virus A; 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: 9
• 化学式量合計: 350086.04

構造登録者

Battles, M.B.,McLellan, J.S. (登録日: 2017-06-05, 公開日: 2017-12-06, 最終更新日: 2024-11-13)

主引用文献

Tian, D.,Battles, M.B.,Moin, S.M.,Chen, M.,Modjarrad, K.,Kumar, A.,Kanekiyo, M.,Graepel, K.W.,Taher, N.M.,Hotard, A.L.,Moore, M.L.,Zhao, M.,Zheng, Z.Z.,Xia, N.S.,McLellan, J.S.,Graham, B.S.
Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein.
Nat Commun, 8:1877-1877, 2017

PubMed Abstract: A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.

PubMed: 29187732
DOI: 10.1038/s41467-017-01858-w

実験手法

X-RAY DIFFRACTION (3.4 Å)