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PMID: 10698638 Published · ppublish English Journal Article

Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion.

Journal of molecular biology ·Vol. 296 ·No. 5 ·2000-03-10 ·Pages 1353-65

Peisajovich SG, Samuel O, Shai Y

Abstract

Viral fusion proteins contain a highly hydrophobic segment, named the fusion peptide, which is thought to be responsible for the merging of the cellular and viral membranes. Paramyxoviruses are believed to contain a single fusion peptide at the N terminus of the F1 protein. However, here we identified an additional internal segment in the Sendai virus F1 protein (amino acids 214-226) highly homologous to the fusion peptides of HIV-1 and RSV. A synthetic peptide, which includes this region, was found to induce membrane fusion of large unilamellar vesicles, at concentrations where the known N-terminal fusion peptide is not effective. A scrambled peptide as well as several peptides from other regions of the F1 protein, which strongly bind to membranes, are not fusogenic. The functional and structural characterization of this active segment suggest that the F1 protein has an additional internal fusion peptide that could participate in the actual fusion event. The presence of homologous regions in other members of the same family suggests that the concerted action of two fusion peptides, one N-terminal and the other internal, is a general feature of paramyxoviruses.

MeSH Terms
Amino Acid Sequence Circular Dichroism Dimerization Endopeptidase K/metabolism Lipid Metabolism Liposomes/chemistry,metabolism,ultrastructure Membrane Fusion Microscopy, Electron Models, Biological Molecular Sequence Data Peptide Fragments/chemical synthesis,chemistry,metabolism Protein Binding Protein Structure, Secondary Respirovirus/chemistry Sequence Homology, Amino Acid Spectrometry, Fluorescence Structure-Activity Relationship Thermodynamics Vacuoles/chemistry,metabolism,ultrastructure Viral Fusion Proteins/chemical synthesis,chemistry,metabolism
Chemicals
Liposomes Peptide Fragments Viral Fusion Proteins Endopeptidase K
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Peisajovich S G
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Samuel O
Shai Y
References (78)
78 references, click to expand
  1. Liposome destabilization induced by the HIV-1 fusion peptide effect of a single amino acid substitution.
    FEBS Lett. 1995 Apr 3;362(2):243-6 PMID: 7720880
  2. Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain.
    Mol Cell. 1998 Nov;2(5):605-16 PMID: 9844633
  3. Interaction of the HIV-1 fusion peptide with phospholipid vesicles: different structural requirements for fusion and leakage.
    Biochemistry. 1994 Mar 22;33(11):3201-9 PMID: 8136355
  4. Dilation of the influenza hemagglutinin fusion pore revealed by the kinetics of individual cell-cell fusion events.
    J Cell Biol. 1996 Oct;135(1):63-71 PMID: 8858163
  5. Orientation into the lipid bilayer of an asymmetric amphipathic helical peptide located at the N-terminus of viral fusion proteins.
    Biochim Biophys Acta. 1990 Nov 16;1029(2):267-73 PMID: 2245211
  6. Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A resolution.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2662-7 PMID: 10077567
  7. Mechanisms of membrane fusion.
    Annu Rev Biophys Biomol Struct. 1993;22:433-66 PMID: 8347997
  8. Phospholipid interactions of synthetic peptides representing the N-terminus of HIV gp41.
    Biochemistry. 1990 Aug 28;29(34):7917-22 PMID: 2261447
  9. Roles in cell-to-cell fusion of two conserved hydrophobic regions in the murine coronavirus spike protein.
    Virology. 1998 May 10;244(2):483-94 PMID: 9601516
  10. Membrane fusion. Anchors aweigh.
    Curr Biol. 1994 Jun 1;4(6):551-4 PMID: 7922379
  11. The crystal structure of the SIV gp41 ectodomain at 1.47 A resolution.
    J Struct Biol. 1999 Jun 15;126(2):131-44 PMID: 10388624
  12. Hydrophobic binding of the ectodomain of influenza hemagglutinin to membranes occurs through the "fusion peptide".
    J Biol Chem. 1989 Apr 15;264(11):6459-64 PMID: 2703499
  13. Direct evidence that the N-terminal heptad repeat of Sendai virus fusion protein participates in membrane fusion.
    J Mol Biol. 1999 Sep 24;292(3):531-46 PMID: 10497019
  14. Membrane fusion by peptide analogues of influenza virus haemagglutinin.
    J Gen Virol. 1988 Aug;69 ( Pt 8):1847-57 PMID: 3404116
  15. Structural and functional characterization of the alpha 5 segment of Bacillus thuringiensis delta-endotoxin.
    Biochemistry. 1993 Apr 6;32(13):3429-36 PMID: 8384882
  16. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus.
    Cell. 1987 Jul 31;50(3):327-8 PMID: 3496970
  17. Entry mechanisms of enveloped viruses. Implications for fusion of intracellular membranes.
    Biosci Rep. 1989 Jun;9(3):273-305 PMID: 2673423
  18. pH- and ionic strength-dependent fusion of phospholipid vesicles induced by pardaxin analogues or by mixtures of charge-reversed peptides.
    Biochemistry. 1993 Apr 6;32(13):3291-7 PMID: 8461295
  19. Mutational analysis of the candidate internal fusion peptide of the avian leukosis and sarcoma virus subgroup A envelope glycoprotein.
    J Virol. 1998 Apr;72(4):3259-67 PMID: 9525653
  20. A synthetic peptide corresponding to a conserved heptad repeat domain is a potent inhibitor of Sendai virus-cell fusion: an emerging similarity with functional domains of other viruses.
    EMBO J. 1995 Nov 15;14(22):5524-31 PMID: 8521809
  21. Sequence determination of the Sendai virus fusion protein gene.
    J Gen Virol. 1985 Feb;66 ( Pt 2):317-31 PMID: 2981971
  22. Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation.
    Proc Natl Acad Sci U S A. 1978 Jun;75(6):2737-40 PMID: 208074
  23. Effects of the 'fusion peptide' from measles virus on the structure of N-methyl dioleoylphosphatidylethanolamine membranes and their fusion with Sendai virus.
    Biochim Biophys Acta. 1991 May 31;1065(1):49-53 PMID: 1646029
  24. Paramyxovirus fusion protein: characterization of the core trimer, a rod-shaped complex with helices in anti-parallel orientation.
    Virology. 1999 Feb 1;254(1):147-59 PMID: 9927582
  25. Photolabeling identifies a putative fusion domain in the envelope glycoprotein of rabies and vesicular stomatitis viruses.
    J Biol Chem. 1995 Jul 21;270(29):17575-81 PMID: 7615563
  26. Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):3810-4 PMID: 1315040
  27. Influenza hemagglutinin assumes a tilted conformation during membrane fusion as determined by attenuated total reflection FTIR spectroscopy.
    EMBO J. 1995 Nov 15;14(22):5514-23 PMID: 8521808
  28. Interaction of peptides with sequences from the Newcastle disease virus fusion protein heptad repeat regions.
    J Virol. 1999 Jul;73(7):5945-56 PMID: 10364347
  29. Synthesis of the antibacterial peptide cecropin A (1-33).
    Biochemistry. 1982 Sep 28;21(20):5020-31 PMID: 6814482
  30. Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations.
    J Biol Chem. 1991 Aug 25;266(24):16120-7 PMID: 1714906
  31. Aggregation and organization of pardaxin in phospholipid membranes. A fluorescence energy transfer study.
    J Biol Chem. 1992 Apr 5;267(10):6502-9 PMID: 1551864
  32. Melittin binding to mixed phosphatidylglycerol/phosphatidylcholine membranes.
    Biochemistry. 1990 Jan 9;29(1):52-8 PMID: 2322549
  33. A fusion-defective mutant of the vesicular stomatitis virus glycoprotein.
    J Virol. 1990 Oct;64(10):4907-13 PMID: 2168975
  34. Core structure of gp41 from the HIV envelope glycoprotein.
    Cell. 1997 Apr 18;89(2):263-73 PMID: 9108481
  35. Effect of nonpolar substitutions of the conserved Phe11 in the fusion peptide of HIV-1 gp41 on its function, structure, and organization in membranes.
    Biochemistry. 1999 Aug 31;38(35):11359-71 PMID: 10471286
  36. Use of resonance energy transfer to monitor membrane fusion.
    Biochemistry. 1981 Jul 7;20(14):4093-9 PMID: 7284312
  37. Synthesis, location, and lateral mobility of fluorescently labeled ubiquinone 10 in mitochondrial and artificial membranes.
    Biochemistry. 1989 Apr 18;28(8):3168-76 PMID: 2742832
  38. Effect of amphipathic peptides with different alpha-helical contents on liposome-fusion.
    Biochim Biophys Acta. 1992 Jan 10;1103(1):157-62 PMID: 1730016
  39. Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4319-24 PMID: 10200260
  40. Vesicular stomatitis virus glycoprotein mutations that affect membrane fusion activity and abolish virus infectivity.
    J Virol. 1995 Mar;69(3):1435-43 PMID: 7853475
  41. Membrane-induced step in the activation of Sendai virus fusion protein.
    J Mol Biol. 1999 Jan 15;285(2):609-25 PMID: 9878433
  42. Determination of the equilibrium micelle-inserting position of the fusion peptide of gp41 of human immunodeficiency virus type 1 at amino acid resolution by exchange broadening of amide proton resonances.
    J Biomol NMR. 1998 Nov;12(4):549-52 PMID: 9862130
  43. Interaction of fluorescently labeled analogues of the amino-terminal fusion peptide of Sendai virus with phospholipid membranes.
    J Biol Chem. 1994 May 27;269(21):15124-31 PMID: 8195149
  44. Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers.
    J Biol Chem. 1991 Dec 15;266(35):23769-75 PMID: 1748653
  45. Surface density determination in membranes by fluorescence energy transfer.
    Biochemistry. 1978 Nov 28;17(24):5241-8 PMID: 728398
  46. Viral and cellular membrane fusion proteins.
    Annu Rev Physiol. 1990;52:675-97 PMID: 2184772
  47. Two disulfide-linked polypeptide chains constitute the active F protein of paramyxoviruses.
    Virology. 1977 Jul 1;80(1):54-66 PMID: 195398
  48. Lipid membrane fusion induced by the human immunodeficiency virus type 1 gp41 N-terminal extremity is determined by its orientation in the lipid bilayer.
    J Virol. 1996 Jan;70(1):298-304 PMID: 8523539
  49. A leucine zipper motif in the ectodomain of Sendai virus fusion protein assembles in solution and in membranes and specifically binds biologically-active peptides and the virus.
    Biochemistry. 1997 Dec 9;36(49):15451-62 PMID: 9398274
  50. Structure-function study of a heptad repeat positioned near the transmembrane domain of Sendai virus fusion protein which blocks virus-cell fusion.
    J Biol Chem. 1998 Oct 16;273(42):27182-90 PMID: 9765238
  51. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein.
    J Virol. 1992 Dec;66(12):7309-18 PMID: 1433520
  52. Phosphatidylinositol-dependent membrane fusion induced by a putative fusogenic sequence of Ebola virus.
    J Virol. 1998 Mar;72(3):1775-81 PMID: 9499027
  53. Structure of influenza haemagglutinin at the pH of membrane fusion.
    Nature. 1994 Sep 1;371(6492):37-43 PMID: 8072525
  54. Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study.
    J Biol Chem. 1997 May 23;272(21):13496-505 PMID: 9153194
  55. Correlation between fusogenicity of synthetic modified peptides corresponding to the NH2-terminal extremity of simian immunodeficiency virus gp32 and their mode of insertion into the lipid bilayer: an infrared spectroscopy study.
    J Virol. 1994 Feb;68(2):1139-48 PMID: 8289343
  56. Ordered conformation of polypeptides and proteins in acidic dodecyl sulfate solution.
    Biochemistry. 1981 Feb 3;20(3):566-70 PMID: 6111337
  57. Minimal aggregate size and minimal fusion unit for the first fusion pore of influenza hemagglutinin-mediated membrane fusion.
    Biophys J. 2000 Jan;78(1):227-45 PMID: 10620288
  58. Channel formation properties of synthetic pardaxin and analogues.
    J Biol Chem. 1990 Nov 25;265(33):20202-9 PMID: 1700783
  59. Studies on the mechanism of membrane fusion: site-specific mutagenesis of the hemagglutinin of influenza virus.
    J Cell Biol. 1986 Jan;102(1):11-23 PMID: 3753607
  60. Lipid polymorphism and protein-lipid interactions.
    Biochim Biophys Acta. 1998 Nov 10;1376(3):353-68 PMID: 9804988
  61. Similar structural models of the transmembrane proteins of Ebola and avian sarcoma viruses.
    Cell. 1996 May 17;85(4):477-8 PMID: 8653783
  62. Atomic structure of the ectodomain from HIV-1 gp41.
    Nature. 1997 May 22;387(6631):426-30 PMID: 9163431
  63. Retrovirus envelope domain at 1.7 angstrom resolution.
    Nat Struct Biol. 1996 May;3(5):465-9 PMID: 8612078
  64. Insertion of a coiled-coil peptide from influenza virus hemagglutinin into membranes.
    Science. 1994 Oct 14;266(5183):274-6 PMID: 7939662
  65. Identification of the fusion peptide of primate immunodeficiency viruses.
    Science. 1989 May 12;244(4905):694-7 PMID: 2541505
  66. Studies on the fusion peptide of a paramyxovirus fusion glycoprotein: roles of conserved residues in cell fusion.
    J Virol. 1992 Apr;66(4):2443-55 PMID: 1548771
  67. Structural basis for paramyxovirus-mediated membrane fusion.
    Mol Cell. 1999 Mar;3(3):309-19 PMID: 10198633
  68. A peptide from the heptad repeat of human immunodeficiency virus gp41 shows both membrane binding and coiled-coil formation.
    Biochemistry. 1995 Oct 17;34(41):13390-7 PMID: 7577925
  69. Trypsin action on the growth of Sendai virus in tissue culture cells. 3. Structural difference of Sendai viruses grown in eggs and tissue culture cells.
    J Virol. 1973 Dec;12(6):1457-65 PMID: 4357516
  70. pH-dependent pore formation properties of pardaxin analogues.
    J Biol Chem. 1991 Nov 25;266(33):22346-54 PMID: 1939258
  71. Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides.
    Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9134-9 PMID: 9689046
  72. Membrane fusion induced by the HIV type 1 fusion peptide: modulation by factors affecting glycoprotein 41 activity and potential anti-HIV compounds.
    AIDS Res Hum Retroviruses. 1997 Sep 20;13(14):1203-11 PMID: 9310287
  73. Protein-mediated membrane fusion.
    Annu Rev Biophys Biophys Chem. 1989;18:187-211 PMID: 2660823
  74. Membrane fusion proteins of enveloped animal viruses.
    Q Rev Biophys. 1983 May;16(2):151-95 PMID: 6359230
  75. The ectodomain of HA2 of influenza virus promotes rapid pH dependent membrane fusion.
    J Mol Biol. 1999 Feb 19;286(2):489-503 PMID: 9973566
  76. Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product.
    J Virol. 1983 Jun;46(3):920-36 PMID: 6304351
  77. A mechanism of protein-mediated fusion: coupling between refolding of the influenza hemagglutinin and lipid rearrangements.
    Biophys J. 1998 Sep;75(3):1384-96 PMID: 9726939
  78. A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 PMID: 1729720
Article Info
Journal
Journal of molecular biology
Abbr.
J Mol Biol
ISSN
0022-2836
DOI
10.1006/jmbi.2000.3543
Published
2000-03-10
Pages
1353-65
Language
English
Region
England
NLM ID
2985088R
PMCID
PMC7127493
Subset
IM
External Links
PubMed source DOI: 10.1006/jmbi.2000.3543 PMC Full Text View journal details
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