Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding - PubMed (original) (raw)

. 1988 Sep 22;335(6188):363-6.

doi: 10.1038/335363a0.

Affiliations

• PMID: 2843773
• DOI: 10.1038/335363a0

Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding

L K Clayton et al. Nature. 1988.

Abstract

Human CD4 is the receptor for the gp120 envelope glycoprotein of human immunodeficiency virus and is essential for virus entry into the host cell. Sequence analysis of CD4 has suggested an evolutionary origin from a structure with four immunoglobulin-related domains. Only the two NH2-terminal domains are required to mediate gp120 binding. The extracellular segment of murine CD4 has an overall 50% identity with its human counterpart at the amino-acid level, but fails to bind gp120. To define those residues of human CD4 critical for gp120 binding, we have taken advantage of this species difference and substituted all non-conserved murine for human CD4 residues between amino-acid positions 27-167. We used oligonucleotide-directed mutagenesis to create each of 16 individual mutant human CD4 molecules containing from 1-4 amino-acid substitutions. Introduction of as few as three amino acids into corresponding positions of human CD4 abrogates gp120 binding. Furthermore, these critical residues are located in domain I with a contribution from domain II. Modelling studies using the three-dimensional coordinates of the V kappa Bence-Jones REI homodimer localize the site in domain I to the C" beta strand within CDR2 but projecting away from the homologues of principle antigen-binding regions CDR 1 and 3.

PubMed Disclaimer

Similar articles

• Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding.
  Clayton LK, Sieh M, Pious DA, Reinherz EL. Clayton LK, et al. Nature. 1989 Jun 15;339(6225):548-51. doi: 10.1038/339548a0. Nature. 1989. PMID: 2543930
• The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4.
  Landau NR, Warton M, Littman DR. Landau NR, et al. Nature. 1988 Jul 14;334(6178):159-62. doi: 10.1038/334159a0. Nature. 1988. PMID: 3260352
• Characterization of CD4 glycoprotein determinant-HIV envelope protein interactions: perspectives for analog and vaccine development.
  Farrar WL, Harel-Bellan A, Ferris DK. Farrar WL, et al. Crit Rev Immunol. 1988;8(4):315-39. Crit Rev Immunol. 1988. PMID: 2850890 Review.
• The effect of low-profile serine substitutions in the V3 loop of HIV-1 gp120 IIIB/LAI on the immunogenicity of the envelope protein.
  Peet NM, McKeating JA, de Souza JB, Roitt IM, Delves PJ, Lund T. Peet NM, et al. Virology. 1998 Nov 10;251(1):59-70. doi: 10.1006/viro.1998.9392. Virology. 1998. PMID: 9813203
• The CD4 receptor for the AIDS virus.
  Weiss RA, Clapham PR, McClure M, Marsh M. Weiss RA, et al. Biochem Soc Trans. 1989 Aug;17(4):644-7. doi: 10.1042/bst0170644. Biochem Soc Trans. 1989. PMID: 2475372 Review. No abstract available.

Cited by

• Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding.
  Olshevsky U, Helseth E, Furman C, Li J, Haseltine W, Sodroski J. Olshevsky U, et al. J Virol. 1990 Dec;64(12):5701-7. doi: 10.1128/JVI.64.12.5701-5707.1990. J Virol. 1990. PMID: 2243375 Free PMC article.
• Identification of a ligand-binding site in an immunoglobulin fold domain of the Saccharomyces cerevisiae adhesion protein alpha-agglutinin.
  de Nobel H, Lipke PN, Kurjan J. de Nobel H, et al. Mol Biol Cell. 1996 Jan;7(1):143-53. doi: 10.1091/mbc.7.1.143. Mol Biol Cell. 1996. PMID: 8741846 Free PMC article.
• Mouse hepatitis virus strain A59 and blocking antireceptor monoclonal antibody bind to the N-terminal domain of cellular receptor.
  Dveksler GS, Pensiero MN, Dieffenbach CW, Cardellichio CB, Basile AA, Elia PE, Holmes KV. Dveksler GS, et al. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1716-20. doi: 10.1073/pnas.90.5.1716. Proc Natl Acad Sci U S A. 1993. PMID: 8383324 Free PMC article.
• A rat CD4 mutant containing the gp120-binding site mediates human immunodeficiency virus type 1 infection.
  Simon JH, Somoza C, Schockmel GA, Collin M, Davis SJ, Williams AF, James W. Simon JH, et al. J Exp Med. 1993 Apr 1;177(4):949-54. doi: 10.1084/jem.177.4.949. J Exp Med. 1993. PMID: 8459222 Free PMC article.
• Mutational analysis of the virus and monoclonal antibody binding sites in MHVR, the cellular receptor of the murine coronavirus mouse hepatitis virus strain A59.
  Wessner DR, Shick PC, Lu JH, Cardellichio CB, Gagneten SE, Beauchemin N, Holmes KV, Dveksler GS. Wessner DR, et al. J Virol. 1998 Mar;72(3):1941-8. doi: 10.1128/JVI.72.3.1941-1948.1998. J Virol. 1998. PMID: 9499047 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program