title: Local structural properties of the V3 loop of Thailand HIV-1 isolate.
abstract: The model of locally accurate conformation for the HIV-Thailand principal neutralizing determinant (PND) located within the V3 loop of the virus envelope protein gp120 was built in terms of NMR spectroscopy data. To this end, the NMR-based conformational analysis of synthetic molecule representing the peptide copy of the fragment under study was carried out using the published sequential d connectivity data and values of spin-spin coupling constants. As a result, (i) the local structure for the V3 loop from Thailand isolate was determined, (ii) the conformations of its irregular segments were analyzed, and the secondary structure elements identified, (iii) the ensemble of conformers matching the experimental and theoretical data was derived for the stretch forming the neutralizing epitope of the HIV-Thailand PND, (iv) to estimate the probability of realizing each of these conformers in solution, the results obtained were collated with the X-ray data for corresponding segments in synthetic molecules imitating the central region of the HIV-MN PND as well as for homologous segments 39-44 in Bence-Jonce REI protein (BJRP), 41-46 in immunoglobulin lambda (Ig lambda), and 50-55 in beta-chain of horse hemoglobin (HH), (v) to find the conserved structural motifs inside diverse HIV-1 isolates, the structure determined was compared with the one derived earlier for the HIV-MN PND from NMR spectroscopy data, (vi) on the basis of all data obtained, the 3D structure model describing the set of biologically relevant conformations, which may present different antigenic determinants to the immune system in various HIV-1 isolates, was proposed for the immunogenic crown of the V3 loop. The results obtained are discussed in conjunction with the data on the structure for the HIV-1 PND reported in literature.
authors.affiliation: Institute of Bioorganic Chemistry, Belarus Academy of Sciences, Kuprevich St., 5/2, 220141 Minsk, Republic of Belarus. andrianov01@yahoo.com
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Andrianov
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D000939:Epitopes / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013785:Thailand; D013816:Thermodynamics
chemical_list: D000939:Epitopes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments