title: A conformational switch is associated with receptor affinity in peptides derived from the CD4-binding domain of gp120 from HIV I.
abstract: A 15-residue region within the CD4-binding domain of gp120 from HIV I was identified with use of folding algorithms as conserving the potential for forming a particular secondary structure throughout 11 sequenced HIV strains. The region chosen has a potential for forming both beta-sheet and alpha-helix; the helical form would be amphipathic with the five hydrophobic residues all totally or functionally conserved. Five peptides were synthesized corresponding to this region in strain LAV and the strain most highly divergent from it in primary structure (Z3) plus three additional peptides with critical substitutions in the LAV sequence. The conformation of these five peptides was examined under various conditions with circular dichroism, and the results were compared with the ability of each peptide to bind to a CD4-expressing strain of HeLa cells (HeLa T4). In solution, the unmodified peptides exhibit a bistable structure, existing as beta-sheet in dilute buffer and converting to alpha-helix under more apolar conditions. The transition is reversible and sharp, occurring at a particular point in the polar/apolar gradient with virtually no intermediate state. The ability to undergo this bistable flip is closely associated with binding ability, amino acid substitutions that eliminate binding ability also eliminating the switch, and vice versa. The transition thus may reflect conformational changes occurring in this region of gp120 as it binds to the CD4 receptor.
authors.affiliation: Institute of Experimental Pathology, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Reed
authors.forename: V
authors.initials: V
authors.lastname: Kinzel
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000737:chemistry* / Q000276:immunology; D002942:Circular Dichroism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000032:analysis* / Q000276:immunology; D006367:HeLa Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015728:Receptors, HIV / Q000737:chemistry* / Q000276:immunology; D012995:Solubility
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV