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Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site.
- Source :
-
Nature Biotechnology . Jul2017, Vol. 35 Issue 7, p667-671. 5p. 1 Diagram, 3 Graphs. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10870156
- Volume :
- 35
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Nature Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 124050037
- Full Text :
- https://doi.org/10.1038/nbt.3907