6IW2

Crystal structure of 5A ScFv in complex with YFV-17D sE in prefusion state

6IW2 の概要

• エントリーDOI: 10.2210/pdb6iw2/pdb
• 分子名称: Envelope protein E, Heavy chain of monoclonal antibody 5A, Light chain of monoclonal antibody 5A (3 entities in total)
• 機能のキーワード: yellow fever virus, neutralizing monoclonal antibody, envelope protein, flavivirus, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Yellow fever virus (strain 17D vaccine) (YFV); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 410867.59

構造登録者

Lu, X.S.,Xiao, H.X.,Li, S.H.,Pang, X.F. (登録日: 2018-12-04, 公開日: 2019-02-13)

主引用文献

Lu, X.,Xiao, H.,Li, S.,Pang, X.,Song, J.,Liu, S.,Cheng, H.,Li, Y.,Wang, X.,Huang, C.,Guo, T.,Ter Meulen, J.,Daffis, S.,Yan, J.,Dai, L.,Rao, Z.,Klenk, H.D.,Qi, J.,Shi, Y.,Gao, G.F.
Double Lock of a Human Neutralizing and Protective Monoclonal Antibody Targeting the Yellow Fever Virus Envelope.
Cell Rep, 26:438-446.e5, 2019

PubMed Abstract: Yellow fever virus (YFV), a deadly human pathogen, is the prototype of the genus Flavivirus. Recently, YFV re-emerged in Africa and Brazil, leading to hundreds of deaths, with some cases imported to China. Prophylactic or therapeutic countermeasures are urgently needed. Previously, several human monoclonal antibodies against YFV were screened out by phage display. Here, we find that one of them, 5A, exhibits high neutralizing potency and good protection. Crystallographic analysis of the YFV envelope (E) protein in its pre- and post-fusion states shows conformations similar to those observed in other E proteins of flaviviruses. Furthermore, the structures of 5A in complex with the E protein in both states are resolved, revealing an invariant recognition site. Structural analysis and functional data suggest that 5A has high neutralization potency because it interferes with virus entry by preventing both virus attachment and fusion. These findings will be instrumental for immunogen or inhibitor design.

PubMed: 30625326
DOI: 10.1016/j.celrep.2018.12.065

実験手法

X-RAY DIFFRACTION (2.9 Å)