It is not known how membrane fusion proteins that function at neutral pH, for example the human immunodeficiency virus envelope (Env) glycoprotein and intracellular fusion machines, are activated for target bilayer binding. We have addressed this question using a soluble oligomeric form of an avian retroviral Env glycoprotein (API) and soluble forms of its receptor. Binding of soluble receptor to API induces API to bind to liposomes composed of phosphatidylcholine and cholesterol at neutral pH. Liposome binding only occurs at fusion permissive temperatures (T > 20°C), is complete between 2 to 5 min at 37°C, and is stable to high salt, carbonate, and urea. Liposome binding is mediated by the ectodomain of the transmembrane subunit of API, and a mutant with a Val to Glu substitution in the Env fusion peptide (located in the ectodomain of the transmembrane subunit) shows significantly reduced liposome binding. Moreover, under conditions of equivalent binding to API, a mutant receptor that does not support infection (Zingler, K., and J.A.T. Young. 1996. J. Virol. 70:7510–7516) does not induce significant liposome binding. Our results indicate that a highly specific interaction between an avian retroviral Env and its receptor activates the retroviral glycoprotein for target bilayer binding at neutral pH in much the same way as low pH activates the influenza hemagglutinin. Our findings are discussed in terms of the mechanisms of viral and cellular fusion proteins that function at neutral pH.
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15 December 1997
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December 15 1997
Activation of a Retroviral Membrane Fusion Protein: Soluble Receptor-induced Liposome Binding of the ALSV Envelope Glycoprotein
Lorraine D. Hernandez,
Lorraine D. Hernandez
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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Reuben J. Peters,
Reuben J. Peters
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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Sue E. Delos,
Sue E. Delos
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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John A.T. Young,
John A.T. Young
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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David A. Agard,
David A. Agard
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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Judith M. White
Judith M. White
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
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Lorraine D. Hernandez
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
Reuben J. Peters
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
Sue E. Delos
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
John A.T. Young
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
David A. Agard
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
Judith M. White
*Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; ‡Department of Biochemistry and Biophysics, §Howard Hughes Medical Institute, University of California, San Francisco, California 94143; and ‖Department of Microbiology and Molecular Genetics, Harvard Medical School, Cambridge, Massachusetts 02138
Work in Dr. White's laboratory was supported by a grant from the National Institutes of Health (A122470). L.D. Hernandez was supported in part by a predoctoral fellowship from the Howard Hughes Medical Institute. D.A. Agard is an Investigator of the Howard Hughes Medical Institute.
Address all correspondence to Judith M. White, Department of Cell Biology, University of Virginia, Health Sciences Center, Box 439, Charlottesville, VA 22908. Tel.: (804) 924-2593. Fax: (804) 982-3912. e-mail: [email protected]
Received:
August 11 1997
Revision Received:
September 19 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 139 (6): 1455–1464.
Article history
Received:
August 11 1997
Revision Received:
September 19 1997
Citation
Lorraine D. Hernandez, Reuben J. Peters, Sue E. Delos, John A.T. Young, David A. Agard, Judith M. White; Activation of a Retroviral Membrane Fusion Protein: Soluble Receptor-induced Liposome Binding of the ALSV Envelope Glycoprotein . J Cell Biol 15 December 1997; 139 (6): 1455–1464. doi: https://doi.org/10.1083/jcb.139.6.1455
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