title: Mutations in the membrane-spanning domain of the human immunodeficiency virus envelope glycoprotein that affect fusion activity.
abstract: A chimeric protein consisting of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) ectodomain joined to the transmembrane and cytoplasmic-tail domains of vesicular stomatitis virus G protein lost the ability to fuse CD4+ HeLa cells yet was transported to the cell surface and cleaved normally. These results suggested some critical role of the HIV gp41 transmembrane or cytoplasmic domain in fusion. Subsequent mutagenic analysis of the HIV-1 Env transmembrane domain revealed that the sequence of amino acid residues from positions 696 to 707 of the transmembrane domain was important for fusion function but was not required for anchoring of the Env protein in the lipid bilayer or for transport to the cell surface. Further analysis indicated that the basic residues at positions 696 and 707 were critical for membrane fusion activity, as was the spacing between these residues. These results demonstrate that in addition to providing an anchoring function, the specific amino acid sequence in the transmembrane domain plays a crucial role in the membrane fusion process.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: R J
authors.initials: RJ
authors.lastname: Owens
authors.forename: C
authors.initials: C
authors.lastname: Burke
authors.forename: J K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D001483:Base Sequence; D002459:Cell Fusion; D004252:DNA Mutational Analysis; D015686:Gene Products, env / Q000235:genetics*; D015700:HIV Envelope Protein gp41 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: C028391:G protein, vesicular stomatitis virus; D015686:Gene Products, env; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins