Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding.
The binding of the CD4 receptor by the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein is important for virus entry and cytopathic effect. To investigate the CD4-binding region of the gp120 glycoprotein, we altered gp120 amino acids, excluding cysteines, that are conserved among the primate immunodeficiency viruses utilizing the CD4 receptor. Changes in two hydrophobic regions (Thr-257 in conserved region 2 and Trp-427 in conserved region 4) and two hydrophilic regions (Asp-368 and Glu-370 in conserved region 3 and Asp-457 in conserved region 4) resulted in significant reductions in CD4 binding. For most of the mutations affecting these residues, the observed effects on CD4 binding did not apparently result from global conformational disruption of the gp120 molecule, as assessed by measurements of precursor processing, subunit association, and monoclonal antibody recognition. The two hydrophilic regions exhibit a strong propensity for beta-turn formation, are predicted to act as efficient B-cell epitopes, and are located adjacent to hypervariable, glycosylated regions. This study defines a small number of gp120 residues important for CD4 binding, some of which might constitute attractive targets for immunologic intervention.
Olshevsky
U
U
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Helseth
E
E
Furman
C
C
Li
J
J
Haseltine
W
W
Sodroski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D015498:HIV-2 / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014162:Transfection
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120