Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Jan 1;175(1):301–304. doi: 10.1084/jem.175.1.301

Construction of a binding site for human immunodeficiency virus type 1 gp120 in rat CD4

PMCID: PMC2119094  PMID: 1730924

Abstract

The human immunodeficiency virus (HIV-1) infects T lymphocytes via an interaction between the virus envelope glycoprotein gp120 and the CD4 antigen of T helper cells. Previous studies demonstrated that mutations in various regions of CD4 domain 1 lead to the loss of gp120 binding. In the present study the gp120 binding site was constructed in rat CD4 by replacing rat with human CD4 sequence. A series of mutants was constructed the best of which bound gp120 with an affinity only twofold less than that of human CD4. The data indicate that the gp120 binding site of human CD4 is constituted by residues 33-58 of domain 1.

Full Text

The Full Text of this article is available as a PDF (391.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arthos J., Deen K. C., Chaikin M. A., Fornwald J. A., Sathe G., Sattentau Q. J., Clapham P. R., Weiss R. A., McDougal J. S., Pietropaolo C. Identification of the residues in human CD4 critical for the binding of HIV. Cell. 1989 May 5;57(3):469–481. doi: 10.1016/0092-8674(89)90922-7. [DOI] [PubMed] [Google Scholar]
  2. Ashkenazi A., Presta L. G., Marsters S. A., Camerato T. R., Rosenthal K. A., Fendly B. M., Capon D. J. Mapping the CD4 binding site for human immunodeficiency virus by alanine-scanning mutagenesis. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7150–7154. doi: 10.1073/pnas.87.18.7150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brodsky M. H., Warton M., Myers R. M., Littman D. R. Analysis of the site in CD4 that binds to the HIV envelope glycoprotein. J Immunol. 1990 Apr 15;144(8):3078–3086. [PubMed] [Google Scholar]
  5. Chao B. H., Costopoulos D. S., Curiel T., Bertonis J. M., Chisholm P., Williams C., Schooley R. T., Rosa J. J., Fisher R. A., Maraganore J. M. A 113-amino acid fragment of CD4 produced in Escherichia coli blocks human immunodeficiency virus-induced cell fusion. J Biol Chem. 1989 Apr 5;264(10):5812–5817. [PubMed] [Google Scholar]
  6. Clark S. J., Jefferies W. A., Barclay A. N., Gagnon J., Williams A. F. Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1649–1653. doi: 10.1073/pnas.84.6.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clayton L. K., Hussey R. E., Steinbrich R., Ramachandran H., Husain Y., Reinherz E. L. Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding. Nature. 1988 Sep 22;335(6188):363–366. doi: 10.1038/335363a0. [DOI] [PubMed] [Google Scholar]
  8. Davis S. J., Ward H. A., Puklavec M. J., Willis A. C., Williams A. F., Barclay A. N. High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. J Biol Chem. 1990 Jun 25;265(18):10410–10418. [PubMed] [Google Scholar]
  9. Healey D. G., Dianda L., Buck D., Schroeder K., Truneh A., Sattentau Q. J., Beverley P. C. A highly selected panel of anti-CD4 antibodies fails to induce anti-idiotypic antisera mediating human immunodeficiency virus neutralization. Eur J Immunol. 1991 Jun;21(6):1491–1498. doi: 10.1002/eji.1830210624. [DOI] [PubMed] [Google Scholar]
  10. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  11. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  12. Peterson A., Seed B. Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4. Cell. 1988 Jul 1;54(1):65–72. doi: 10.1016/0092-8674(88)90180-8. [DOI] [PubMed] [Google Scholar]
  13. Ryu S. E., Kwong P. D., Truneh A., Porter T. G., Arthos J., Rosenberg M., Dai X. P., Xuong N. H., Axel R., Sweet R. W. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419–426. doi: 10.1038/348419a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Seed B. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. 1987 Oct 29-Nov 4Nature. 329(6142):840–842. doi: 10.1038/329840a0. [DOI] [PubMed] [Google Scholar]
  15. Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wang J. H., Yan Y. W., Garrett T. P., Liu J. H., Rodgers D. W., Garlick R. L., Tarr G. E., Husain Y., Reinherz E. L., Harrison S. C. Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature. 1990 Nov 29;348(6300):411–418. doi: 10.1038/348411a0. [DOI] [PubMed] [Google Scholar]
  17. Wilks D., Walker L., O'Brien J., Habeshaw J., Dalgleish A. Differences in affinity of anti-CD4 monoclonal antibodies predict their effects on syncytium induction by human immunodeficiency virus. Immunology. 1990 Sep;71(1):10–15. [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES