Identification of membrane anchorage domains of the HIV-1 gp160 envelope glycoprotein precursor.
The gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) contains a hydrophobic membrane-spanning domain that serves to anchor the gp120-gp41 complex on the surface of infected cells and virions. To study the requirements for membrane anchorage, conservative amino acid substitutions in three residues at a time were made within this hydrophobic gp41 region. The complete gp160 precursor as well as the gp120 exterior envelope glycoprotein were exported into the supernatant of expressing cells for two mutants with amino acid substitutions in residues 687-689 and 697-699. The soluble gp160 molecules exhibited a binding ability for CD4 on the surface of SupT1 cells that was 33-36% that of the soluble gp120 glycoproteins. These results implicate residues 687-689 and 697-699 as important components of the stop-transfer signal that anchors the gp160 envelope glycoprotein precursor in the membrane. The data also suggest that characteristics in addition to hydrophobicity are required for stop-transfer signals.
Gabuzda
D
D
Laboratory of Human Retrovirology, Dana-Farber Cancer Institute, Boston, MA 02115.
Olshevsky
U
U
Bertani
P
P
Haseltine
W A
WA
Sodroski
J
J
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D015726:Giant Cells; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D015531:Radioimmunoprecipitation Assay; D014162:Transfection
D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011498:Protein Precursors