The role of the membrane-spanning domain sequence in glycoprotein-mediated membrane fusion.
The role of glycoprotein membrane-spanning domains in the process of membrane fusion is poorly understood. It has been demonstrated that replacing all or part of the membrane-spanning domain of a viral fusion protein with sequences that encode signals for glycosylphosphatidylinositol linkage attachment abrogates membrane fusion activity. It has been suggested, however, that the actual amino acid sequence of the membrane-spanning domain is not critical for the activity of viral fusion proteins. We have examined the function of Moloney murine leukemia virus envelope proteins with substitutions in the membrane-spanning domain. Envelope proteins bearing substitutions for proline 617 are processed and incorporated into virus particles normally and bind to the viral receptor. However, they possess greatly reduced or undetectable capacities for the promotion of membrane fusion and infectious virus particle formation. Our results imply a direct role for the residues in the membrane-spanning domain of the murine leukemia virus envelope protein in membrane fusion and its regulation. They also support the thesis that membrane-spanning domains possess a sequence-dependent function in other protein-mediated membrane fusion events.
Taylor
G M
GM
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
Sanders
D A
DA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011991:Receptors, Virus / Q000378:metabolism; D019065:Virus Assembly
D015686:Gene Products, env; D006023:Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; D011392:Proline