       Document 0117
 DOCN  M9550117
 TI    Local and global structural properties of the HIV-MN V3 loop.
 DT    9505
 AU    Catasti P; Fontenot JD; Bradbury EM; Gupta G; Theoretical Biology and
       Biophysics Group, Los Alamos National; Laboratory, New Mexico 87545.
 SO    J Biol Chem. 1995 Feb 3;270(5):2224-32. Unique Identifier : AIDSLINE
       MED/95138191
 AB    Studies of the feasibility of a subunit vaccine to protect against human
       immunodeficiency virus (HIV) infection have principally focused on the
       third variable (V3) loop. The principal neutralizing determinant (PND)
       of HIV-1 is located inside the V3 loop of the surface envelope
       glycoprotein, gp120. However, progress toward a PND-based vaccine has
       been impeded by the amino acid sequence variability in the V3 loops of
       different HIV isolates. Theoretical studies revealed that the
       variability in sequence and structure of the V3 loop is confined to the
       N- and C-terminal sides of the conserved GPG crest. This leaves three
       regions of the V3 loop conserved both in sequence and secondary
       structure. We present the results of NMR studies that test the validity
       of our theoretical predictions. Structural studies are reported for the
       HIV-V3 loop (HIV-MN) in the linear and cyclic (S-S-bridged) forms. For
       the V3 loop sequence of the HIV-MN isolate, the three conserved
       secondary structural elements are as underlined below: turns turn helix
       CTRPNYNKRKRIHIGPGRAFYTTKNIIGTIROAHC Finally, the conformational
       requirement of the PND in the V3 loop-antibody interaction is tested by
       monitoring the monoclonal antibody binding to the HIV-MN V3 loop in the
       linear and cyclic forms by enzyme-linked immunosorbent assay. The
       binding data reveal that the cyclic V3 loop is a better ligand for the
       monoclonal antibodies than the linear form although the latter has the
       same sequence. This means that the monoclonal antibodies recognize the
       PNDs as conformational epitopes.
 DE    Amino Acid Sequence  HIV Antigens/CHEMISTRY  HIV Envelope Protein
       gp120/*CHEMISTRY/IMMUNOLOGY  HIV-1/IMMUNOLOGY/*ULTRASTRUCTURE  Models,
       Molecular  Molecular Sequence Data  Nuclear Magnetic Resonance  Protein
       Structure, Secondary  Solvents  Support, U.S. Gov't, Non-P.H.S.
       Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

