Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef.

ABSTRACT: Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not targeted by current antiviral measures. Here we inhibit Nef function by simultaneously blocking several highly conserved protein interaction surfaces. This strategy, referred to as "wrapping Nef", is based on structure-function analyses that led to the identification of four target sites: (i) SH3 domain interaction, (ii) interference with protein transport processes, (iii) CD4 binding and (iv) targeting to lipid membranes. Screening combinations of Nef-interacting domains, we developed a series of small Nef interacting proteins (NIs) composed of an SH3 domain

SUBMITTER: Breuer S 

PROVIDER: S-EPMC3098852 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature