DI1120002 0.5b anti-HIV antibody complex with the gp120 V3 peptide 1qnz NMR Human immunodeficiency virus 1 / Mus musculus Inferred from homology 10801487 Tugarinov V, Zvi A, Levy R, Hayek Y, Matsushita S, Anglister J Structure 2000 4 8 385-95 CONCLUSIONS: The surface of P1053 that is in contact with the anti-protein antibody 0.5beta is likely to correspond to a solvent-exposed region in the native gp120 molecule. Some residues of this region of gp120 are involved in co-receptor binding, and in discrimination between different chemokine receptors utilized by the protein. Several highly variable residues in the V3 loop limit the specificity of the 0.5beta antibody, helping the virus to escape from the immune system. The highly conserved GPG sequence might have a role in maintaining the beta-hairpin conformation of the V3 loop despite insertions, deletions and mutations in the flanking regions. RESULTS: Virtually complete sidechain assignment of the variable fragment (Fv) of 0.5beta in complex with the V3(IIIB) peptide P1053 (RKSIRIQRGPGRAFVTIG, in single-letter amino acid code) was accomplished and the combining site structure of 0.5beta Fv complexed with P1053 was solved using multidimensional nuclear magnetic resonance (NMR). Five of the six complementarity determining regions (CDRs) of the antibody adopt standard canonical conformations, whereas CDR3 of the heavy chain assumes an unexpected fold. The epitope recognized by 0.5beta encompasses 14 of the 18 P1053 residues. The bound peptide assumes a beta-hairpin conformation with a QRGPGR loop located at the very center of the binding pocket. The Fv and peptide surface areas buried upon binding are 601 A and 743 A(2), respectively, in the 0.5beta Fv-P1053 mean structure. The surface of P1053 interacting with the antibody is more extensive and the V3 peptide orientation in the binding site is significantly different compared with those derived from the crystal structures of a V3 peptide of the HIV-1 MN strain (V3(MN)) complexed to three different anti-peptide antibodies. BACKGROUND: The protein 0.5beta is a potent strain-specific human immunodeficiency virus type 1 (HIV-1) neutralizing antibody raised against the entire envelope glycoprotein (gp120) of the HIV-1(IIIB) strain. The epitope recognized by 0.5beta is located within the third hypervariable region (V3) of gp120. Recently, several HIV-1 V3 residues involved in co-receptor utilization and selection were identified. Chain L was removed as chains H and P represent the biologically relevant interaction. 2 V-set P Envelope protein (Fragment) Disordered Human immunodeficiency virus 1 RKSIRIQRGPGRAFVTIG 18 Q79416 9 26 50% UniRef90_P04578 304 321 secondary structure beta 11 13 secondary structure beta 22 24 pfam PF00516.15 GP120 1 36 H Ig heavy chain V region 102 Ordered Mus musculus VQLQQSGAELVKPGASVKMSCKASGYTFTTYPIEWMKQNHGKSLEWIGNFHPYSDDTNYNEKFKGKAKLTVEKSSSTVYLEFSRLTSDDSAVYYCAI 97 P01750 21 117 82.9% UniRef90_A0A075B5V8 1 97 secondary structure beta 22 26 secondary structure beta 30 31 secondary structure beta 35 44 secondary structure beta 53 59 secondary structure beta 65 71 secondary structure beta 76 77 secondary structure beta 87 92 secondary structure beta 97 105 secondary structure helix 107 109 secondary structure beta 111 117 pfam PF07686.14 V-set 24 117 P The corresponding region of a closely homologous protein has been shown to be disordered in the 297-331 region described in DisProt entry DP00976 (covers 100% of the sequence present in the structure). H The V-set domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF07686). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1ah1.