title: Comparative analysis of the gp120-binding area of murine and human CD4 molecules.
abstract: The structural basis for the difference between human and murine CD4 molecules in binding to HIV envelope protein gp120 has been intensively studied. Eighteen mutant human CD4 molecules were produced by segmental replacement of beta strands and loops in the gp120-binding area of the molecule with corresponding murine sequences or by single amino acid substitutions. Examination of these mutant CD4 molecules for gp120 binding indicated that murine CD4 molecule does not bind gp120 for the following three reasons: (a) The loops flanking the C" strand are longer than their human counterparts, causing significant difference in local tertiary structure; (b) valin, rather than phenylalanine, which is the key amino acid for the binding occupies position 43; (c) amino acids at positions 45 and 46 are different, causing further decrease in binding affinity. Furthermore, the present study indicated that the aromatic ring of Phe43 and the negative charge of Arg59 play key roles in gp120 binding.
authors.affiliation: Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqi
authors.forename: M
authors.initials: M
authors.lastname: Tachibana
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: Y
authors.initials: Y
authors.lastname: Ikegami
authors.forename: S
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.forename: Y Y
authors.initials: YY
authors.lastname: Huang
authors.forename: N
authors.initials: N
authors.lastname: Shinohara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000737:chemistry; D013945:Thymoma; D014162:Transfection; D014407:Tumor Cells, Cultured; D014633:Valine / Q000737:chemistry
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010649:Phenylalanine; D001120:Arginine; D014633:Valine