5KUY

Influenza hemagglutinin H3 A/Hong Kong/1/1968 in complex with designed inhibitor protein HSB.2A

5KUY の概要

• エントリーDOI: 10.2210/pdb5kuy/pdb
• 関連するPDBエントリー: 5KUX
• 分子名称: Hemagglutinin HA1, Hemagglutinin HA2, Designed influenza inhibitor HSB.2A, ... (7 entities in total)
• 機能のキーワード: influenza, inhibitor, complex, design, protein binding
• 由来する生物種: Influenza A virus (strain A/Hong Kong/1/1968 H3N2); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 203993.09

構造登録者

Bernard, S.M.,Wilson, I.A. (登録日: 2016-07-13, 公開日: 2017-06-14, 最終更新日: 2023-10-04)

主引用文献

Strauch, E.M.,Bernard, S.M.,La, D.,Bohn, A.J.,Lee, P.S.,Anderson, C.E.,Nieusma, T.,Holstein, C.A.,Garcia, N.K.,Hooper, K.A.,Ravichandran, R.,Nelson, J.W.,Sheffler, W.,Bloom, J.D.,Lee, K.K.,Ward, A.B.,Yager, P.,Fuller, D.H.,Wilson, I.A.,Baker, D.
Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site.
Nat. Biotechnol., 35:667-671, 2017

PubMed Abstract: Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

PubMed: 28604661
DOI: 10.1038/nbt.3907

実験手法

X-RAY DIFFRACTION (2.598 Å)