4EEF
Crystal structure of the designed inhibitor protein F-HB80.4 in complex with the 1918 influenza virus hemagglutinin.
Summary for 4EEF
| Entry DOI | 10.2210/pdb4eef/pdb |
| Descriptor | Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, F-HB80.4, DESIGNED HEMAGGLUTININ BINDING PROTEIN, ... (5 entities in total) |
| Functional Keywords | immunoglobulin, hemagglutinin, fusion of virus membrane with host membrane, membrane fusion, sialic acid, virion, immune system, immune system-inhibitor complex, immune system/inhibitor |
| Biological source | Influenza A virus More |
| Cellular location | Virion membrane; Single-pass type I membrane protein (Potential): Q9WFX3 Q9WFX3 |
| Total number of polymer chains | 9 |
| Total formula weight | 198733.63 |
| Authors | Dreyfus, C.,Wilson, I.A. (deposition date: 2012-03-28, release date: 2012-06-27, Last modification date: 2020-07-29) |
| Primary citation | 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 Cited by 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: 22634563DOI: 10.1038/nbt.2214 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.704 Å) |
Structure validation
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