Structural basis for the inhibition of HIV-1 Nef by a high-affinity binding single-domain antibody.

ABSTRACT:

Background

The HIV-1 Nef protein is essential for AIDS pathogenesis by its interaction with host cell surface receptors and signaling factors. Despite its critical role as a virulence factor Nef is not targeted by current antiviral strategies.

Results

We have determined the crystal structure of the complex formed by a camelid single-domain antibody fragment, termed sdAb19, bound to HIV-1 Nef together with a stabilizing SH3 domain. sdAb19 forms a stoichiometric 1:1 complex with Nef and binds to a conformationally conserved surface at the C-terminus of Nef that overlaps with functionally important interaction sites involved in Nef-induced perturbations of signaling and trafficking pathways. The antibody fragment binds Nef with low nanomolar affinity, which could be attenuated

SUBMITTER: Lulf S 

PROVIDER: S-EPMC4007562 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature