Characterization of the interaction between peptides derived from the gp120/V3 domain of HIV-1 and the amino terminal of the chemokine receptor CCR5 by NMR spectroscopy and light scattering

We applied static and dynamic light scattering (DLS) to probe the structural and physicochemical determinants of the interaction between the gp120 V3 domain of the human immunodeficiency virus HIV-1 and the amino terminal of the chemokine receptor CCR5 (CCR5-Nt). CCR5-Nt is a co-receptor that infectious HIV strains utilize to gain entry into target cells. Preventing HIV from interacting with these co-receptors prevents viral entry. In this study, we present the first systematic investigation of the size, shape, dynamics, and interactions of self-associating peptide complexes formed by a 13-residue peptide, V3 (from the strain MN), in dilute aqueous solution, using DLS. Nuclear magnetic resonance (NMR) spectra indicate that the free V3 and CCR5-Nt peptides as well as the V3-CCR5-Nt mixture are somehow structured in solution. Also, NMR spectra in combination with peptide titration suggest a weak interaction between the V3 domain and CCR5-Nt. Finally, the NMR data suggest monomeric or self-associating complexes amenable to NMR studies without significant spectral line broadening, for V3, CCR5-Nt, and the V3-CCR5-Nt complex. The monomers or self-associating complexes observed by NMR are not expected to be in exchange with the self-associating complexes observed by dynamic light scattering. Light scattering on exactly the same NMR samples confirms the presence of the complexes that were observed at lower concentrations.