5KUY
Influenza hemagglutinin H3 A/Hong Kong/1/1968 in complex with designed inhibitor protein HSB.2A
Summary for 5KUY
| Entry DOI | 10.2210/pdb5kuy/pdb |
| Related | 5KUX |
| Descriptor | Hemagglutinin HA1, Hemagglutinin HA2, Designed influenza inhibitor HSB.2A, ... (7 entities in total) |
| Functional Keywords | influenza, inhibitor, complex, design, protein binding |
| Biological source | Influenza A virus (strain A/Hong Kong/1/1968 H3N2) More |
| Total number of polymer chains | 9 |
| Total formula weight | 203993.09 |
| Authors | Bernard, S.M.,Wilson, I.A. (deposition date: 2016-07-13, release date: 2017-06-14, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 28604661DOI: 10.1038/nbt.3907 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.598 Å) |
Structure validation
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