4EEF

Crystal structure of the designed inhibitor protein F-HB80.4 in complex with the 1918 influenza virus hemagglutinin.

4EEF の概要

• エントリーDOI: 10.2210/pdb4eef/pdb
• 分子名称: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, F-HB80.4, DESIGNED HEMAGGLUTININ BINDING PROTEIN, ... (5 entities in total)
• 機能のキーワード: immunoglobulin, hemagglutinin, fusion of virus membrane with host membrane, membrane fusion, sialic acid, virion, immune system, immune system-inhibitor complex, immune system/inhibitor
• 由来する生物種: Influenza A virus; 詳細
• 細胞内の位置: Virion membrane; Single-pass type I membrane protein (Potential): Q9WFX3 Q9WFX3
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 198733.63

構造登録者

Dreyfus, C.,Wilson, I.A. (登録日: 2012-03-28, 公開日: 2012-06-27, 最終更新日: 2024-11-27)

主引用文献

Whitehead, T.A.,Chevalier, A.,Song, Y.,Dreyfus, C.,Fleishman, S.J.,De Mattos, C.,Myers, C.A.,Kamisetty, H.,Blair, P.,Wilson, I.A.,Baker, D.
Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing.
Nat.Biotechnol., 30:543-548, 2012

PubMed Abstract: We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.

PubMed: 22634563
DOI: 10.1038/nbt.2214

実験手法

X-RAY DIFFRACTION (2.704 Å)