5KUX

Designed influenza hemagglutinin binding protein HSB.2

Summary for 5KUX

• Entry DOI: 10.2210/pdb5kux/pdb
• Related: 5KUY
• Descriptor: Designed influenza inhibitor protein HSB.2 (2 entities in total)
• Functional Keywords: influenza, inhibitor, designed protein, cystatin, protein binding
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 11017.27

Authors

Lee, P.S.,Bernard, S.M.,Wilson, I.A. (deposition date: 2016-07-13, release date: 2017-06-14, Last modification date: 2023-10-04)

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

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)