Functional role of the zipper motif region of human immunodeficiency virus type 1 transmembrane protein gp41.
To study the functional role of the zipper motif region, located in the N-terminal region of the envelope transmembrane protein of human immunodeficiency virus type 1, a series of vaccinia virus-expressed mutant proteins containing a proline substitution in this region were characterized. All of the mutant proteins showed partial or no inhibition in gp160 cleavage, demonstrated impaired ability of gp120 to associate with gp41, and were unable to mediate syncytium formation with CD4+ cells. Moreover, mutants 580 and 587 secreted excessive gp120 into the medium compared with the wild type. Mutations in this region affected the conformation of the local or proximal sequence but did not alter the conformation conferred by a distal site. These studies reveal the crucial role of the C-terminal segment of the zipper motif region in envelope heterodimeric association and suggest that this sequence forms a gp120 contact site.
Chen
S S
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Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D004252:DNA Mutational Analysis; D000939:Epitopes; D015686:Gene Products, env / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D016350:Leucine Zippers / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014616:Vaccinia virus / Q000235:genetics
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015704:CD4 Antigens; D000939:Epitopes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011498:Protein Precursors