Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site.

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

SUBMITTER: Strauch EM 

PROVIDER: S-EPMC5512607 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature