title: Structure and polymorphism of HIV-1 third variable loops.
abstract: The third variable (V3) loop of HIV-1 surface glycoprotein, gp120, has been the target of neutralizing antibodies. However, sequence variation inside the V3 loop diminishes its effectiveness as a potential vaccine against HIV-1. The elusive nature of the V3 loop structure prompted us to carry out a systematic study on different isolates in an attempt to identify a common structural motif in the V3 loop regardless of the amino acid sequence variability. We have previously determined the structural features of two V3 loops: V3 Thailand and V3 MN. In this paper, we present the structure of two other variants: V3 Haiti and V3 RF. Our results show that similar secondary structures are observed in all the four V3 loops: a GPG(R/K/Q) crest in the center of the neutralizing domain, two extended regions flanking the central crest, and a helical region in the C-terminal domain. For the Haitian V3 loop, we also show how the conserved structural features are masked through a conformational switch encoded in the amino acid sequences on the C-terminal side of the GPGK crest.
authors.affiliation: Theoretical Biology and Biophysics Group, T-10, M/S K710 and the Life Science Division, M/S M881, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
authors.forename: P
authors.initials: P
authors.lastname: Catasti
authors.forename: E M
authors.initials: EM
authors.lastname: Bradbury
authors.forename: G
authors.initials: G
authors.lastname: Gupta
mesh_terms: D000595:Amino Acid Sequence; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D015699:HIV Envelope Protein gp120; D012997:Solvents; D014867:Water; D014270:Trifluoroethanol