title: Contribution of disulfide bonds in the carboxyl terminus of the human immunodeficiency virus type I gp120 glycoprotein to CD4 binding.
abstract: The carboxyl half of the HIV-1 gp120 glycoprotein, which has been implicated in binding to the CD4 receptor, contains two disulfide bonds linking cysteine residues 378-445 and 385-418. To examine the necessity of these disulfide bonds for the formation and/or maintenance of a gp120 glycoprotein competent for CD4 binding, we created mutants of a soluble form of gp120 in which combinations of these cysteine residues were altered. The mutant glycoproteins were examined for export from the expressing cell and for CD4 binding ability. Mutant gp120 molecules lacking both disulfide bonds were not stably expressed or exported. However, mutants for which either disulfide bond could form were exported and were fully competent for CD4 binding. In some cases, the presence of one of the pair of linked cysteines exerted more detrimental effects on export or CD4 binding than did alteration of both cysteines. Thus, the evaluation or the contribution of a particular disulfide bond to a phenotype should include studies in which both cysteines involved in the bond are simultaneously altered.
authors.affiliation: Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: C
authors.initials: C
authors.lastname: Lekutis
authors.forename: U
authors.initials: U
authors.lastname: Olshevsky
authors.forename: C
authors.initials: C
authors.lastname: Furman
authors.forename: M
authors.initials: M
authors.lastname: Thali
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009154:Mutation; D010957:Plasmids; D014162:Transfection
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120