Fusion peptides and the mechanism of viral fusion.

Segments of viral fusion proteins play an important role in viral fusion. They are defined by a number of criteria, including the sensitivity of this region of the viral fusion protein to loss of function as a consequence of mutation. In addition, small model peptides designed to mimic this segment of viral fusion proteins often have some membrane perturbing activity. The properties of viral fusion peptides are quite varied. Many are found at the amino terminus of viral fusion proteins. As isolated peptides, they have been found to form both alpha-helical as well as beta-structure. In addition, some viruses have internal fusion peptides. Just as there are several structural motifs for viral fusion peptides, there are also several mechanisms by which they accelerate the process of membrane fusion. These include the promotion of negative curvature, lowering the rupture tension of the lipid monolayer, acting as an anchor to join the fusion membranes, transmitting a force to the membrane or imparting energy to the system by other means. It is not likely that the fusion peptide can fulfill all of these diverse roles and future studies will elucidate which of these mechanisms is most important for the action of individual viral fusion peptides.

[1]  W. DeGrado,et al.  Membrane binding and conformational properties of peptides representing the NH2 terminus of influenza HA-2. , 1987, The Journal of biological chemistry.

[2]  R. Epand,et al.  Role of the Glu residues of the influenza hemagglutinin fusion peptide in the pH dependence of fusion activity. , 2001, Virology.

[3]  Y. Shin,et al.  A peptide from the heptad repeat of human immunodeficiency virus gp41 shows both membrane binding and coiled-coil formation. , 1995, Biochemistry.

[4]  D. Hammer,et al.  Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation. , 1997, Biophysical journal.

[5]  R. Epand,et al.  Effect of influenza hemagglutinin fusion peptide on lamellar/inverted phase transitions in dipalmitoleoylphosphatidylethanolamine: implications for membrane fusion mechanisms. , 2000, Biochimica et biophysica acta.

[6]  Evan Evans,et al.  Physical properties of surfactant bilayer membranes: thermal transitions, elasticity, rigidity, cohesion and colloidal interactions , 1987 .

[7]  D. Siegel.  The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. , 1999, Biophysical journal.

[8]  S. Peisajovich,et al.  New insights into the mechanism of virus-induced membrane fusion. , 2002, Trends in biochemical sciences.

[9]  B. Lentz,et al.  Effects of hemagglutinin fusion peptide on poly(ethylene glycol)-mediated fusion of phosphatidylcholine vesicles. , 2001, Biochemistry.

[10]  R. Epand,et al.  Oblique membrane insertion of viral fusion peptide probed by neutron diffraction. , 2000, Biochemistry.

[11]  R. Brasseur,et al.  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 , 1994, Journal of virology.

[12]  T. Vorherr,et al.  H+-induced Membrane Insertion of Influenza Virus Hemagglutinin Involves the HA2 Amino-terminal Fusion Peptide but Not the Coiled Coil Region* , 1996, The Journal of Biological Chemistry.

[13]  J. Ruysschaert,et al.  Membrane interactions of mutated forms of the influenza fusion peptide. , 2001, Biochemistry.

[14]  E. Knapp,et al.  Protonation and stability of the globular domain of influenza virus hemagglutinin. , 2002, Biophysical journal.

[15]  I. Wilson,et al.  Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution , 1981, Nature.

[16]  J. Zimmerberg,et al.  Synchronized activation and refolding of influenza hemagglutinin in multimeric fusion machines , 2001, The Journal of cell biology.

[17]  M. Kozlov,et al.  A mechanism of protein-mediated fusion: coupling between refolding of the influenza hemagglutinin and lipid rearrangements. , 1998, Biophysical journal.

[18]  L. Hernandez,et al.  Mutational Analysis of the Candidate Internal Fusion Peptide of the Avian Leukosis and Sarcoma Virus Subgroup A Envelope Glycoprotein , 1998, Journal of Virology.

[19]  R. Epand,et al.  The ectodomain of HA2 of influenza virus promotes rapid pH dependent membrane fusion. , 1999, Journal of molecular biology.

[20]  F S Cohen,et al.  A specific point mutant at position 1 of the influenza hemagglutinin fusion peptide displays a hemifusion phenotype. , 1999, Molecular biology of the cell.

[21]  Qiang Huang,et al.  The Role of the Transmembrane and of the Intraviral Domain of Glycoproteins in Membrane Fusion of Enveloped Viruses , 2000, Bioscience reports.

[22]  S. Peisajovich,et al.  The polar region consecutive to the HIV fusion peptide participates in membrane fusion. , 2000, Biochemistry.

[23]  J. White,et al.  Critical Role for the Cysteines Flanking the Internal Fusion Peptide of Avian Sarcoma/Leukosis Virus Envelope Glycoprotein , 2000, Journal of Virology.

[24]  C. M. Gabrys,et al.  Solid-state nuclear magnetic resonance evidence for an extended beta strand conformation of the membrane-bound HIV-1 fusion peptide. , 2001, Biochemistry.

[25]  R. Duncan,et al.  A new class of fusion‐associated small transmembrane (FAST) proteins encoded by the non‐enveloped fusogenic reoviruses , 2000, The EMBO journal.

[26]  Structural study of the interaction between the SIV fusion peptide and model membranes. , 1996 .

[27]  Y. Shai,et al.  Participation of two fusion peptides in measles virus-induced membrane fusion: emerging similarity with other paramyxoviruses. , 2001, Biochemistry.

[28]  R. Epand.  Lipid polymorphism and protein-lipid interactions. , 1998, Biochimica et biophysica acta.

[29]  L. Chernomordik.  Non-bilayer lipids and biological fusion intermediates. , 1996, Chemistry and physics of lipids.

[30]  R. Chernish,et al.  Effects of double-site mutations of vesicular stomatitis virus glycoprotein G on membrane fusion activity. , 1999, Virology.

[31]  S. Peisajovich,et al.  Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion1 , 2000, Journal of Molecular Biology.

[32]  J L Nieva,et al.  Hydrophobic-at-Interface Regions in Viral Fusion Protein Ectodomains , 2000, Bioscience reports.

[33]  T. Shangguan,et al.  Influenza-virus-liposome lipid mixing is leaky and largely insensitive to the material properties of the target membrane. , 1996, Biochemistry.

[34]  J. Ruysschaert,et al.  Structure and Topology of the Influenza Virus Fusion Peptide in Lipid Bilayers (*) , 1995, The Journal of Biological Chemistry.

[35]  Shih-Hsiung Wu,et al.  Structural Characterizations of Fusion Peptide Analogs of Influenza Virus Hemagglutinin , 2002, The Journal of Biological Chemistry.

[36]  T. Wolfsberg,et al.  Virus-cell and cell-cell fusion. , 1996, Annual review of cell and developmental biology.

[37]  R. Epand,et al.  The 1-127 HA2 construct of influenza virus hemagglutinin induces cell-cell hemifusion. , 2001 .

[38]  J. Ruysschaert,et al.  Membrane orientation of the SIV fusion peptide determines its effect on bilayer stability and ability to promote membrane fusion. , 1994, Biochemical and biophysical research communications.

[39]  Stephen H. White,et al.  Experimentally determined hydrophobicity scale for proteins at membrane interfaces , 1996, Nature Structural Biology.

[40]  J. White,et al.  The Central Proline of an Internal Viral Fusion Peptide Serves Two Important Roles , 2000, Journal of Virology.

[41]  R. Epand,et al.  Relationship between the infectivity of influenza virus and the ability of its fusion peptide to perturb bilayers. , 1994, Biochemical and biophysical research communications.

[42]  R. Brasseur,et al.  Theoretical and functional analysis of the SIV fusion peptide. , 1991, The EMBO journal.

[43]  R. Epand,et al.  Thermal denaturation of influenza virus and its relationship to membrane fusion. , 2002, The Biochemical journal.

[44]  A. Agirre,et al.  Membrane Interface-Interacting Sequences within the Ectodomain of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Putative Role during Viral Fusion , 2000, Journal of Virology.

[45]  J. Skehel,et al.  Structure of influenza haemagglutinin at the pH of membrane fusion , 1994, Nature.

[46]  Lukas K. Tamm,et al.  Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin , 2001, Nature Structural Biology.

[47]  S. Peisajovich,et al.  Sendai virus internal fusion peptide: structural and functional characterization and a plausible mode of viral entry inhibition. , 2000, Biochemistry.