Solution Structure of an Antibody-Bound HIV-1^IIIBV3 Peptide: A Cis Proline Turn Linking Two β-hairpin Strands

Abstract

The refined solution structure of a peptide representing the full epitope of the HIV-1(IIIB) V3 loop in complex with the anti-gp120 antibody Fv fragment was determined using isotope-filtered and isotope-edited NMR. Both the (15)N-labeled peptide in complex with the unlabeled Fv and the unlabeled peptide complexed with the uniformly (15)N,(13)C-labeled Fv were investigated. The backbone of the bound peptide adopts a well defined β-hairpin conformation with two twisted anti-parallel β-strands linked by a type VI tight turn comprising residues RGPG. The central glycine and proline residues of the turn are linked by a cis peptide bond. (15)N{(1)H} NOE measurements demonstrated that the backbone of the bound peptide including the central QRGPGR loop is well ordered in the bound state. The V3 loop peptide solution structure is significantly different from the peptide conformation in the X-ray structures of three anti-peptide antibody/V3(MN) peptide complexes. These differences seem to be dictated by the antibody dependence and HIV strain-specificity of the V3 peptide fold.