Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism
A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we inve...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1744683X_v11_n15_p3003_Vitiello http://hdl.handle.net/20.500.12110/paper_1744683X_v11_n15_p3003_Vitiello |
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paper:paper_1744683X_v11_n15_p3003_Vitiello2023-06-08T16:28:13Z Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism Association reactions Cell membranes Cholesterol Cytology Dynamic light scattering Electron spin resonance spectroscopy Glycoproteins Light scattering Magnetic moments Molecular dynamics Peptides Phospholipids Spin dynamics Viruses Asymmetric perturbations Comparative analysis Herpes simplex virus Molecular dynamics simulations Molecular mechanism Neutron reflectivity Phosphatidylcholine Specific interaction Lipid bilayers Simplexvirus 1-palmitoyl-2-oleoylphosphatidylcholine cholesterol gH625 peptide, Herpes simplex virus type I glycoprotein lipid bilayer peptide phosphatidylcholine sphingomyelin virus envelope protein virus protein chemistry lipid bilayer molecular dynamics protein tertiary structure Cholesterol Glycoproteins Lipid Bilayers Molecular Dynamics Simulation Peptides Phosphatidylcholines Protein Structure, Tertiary Sphingomyelins Viral Envelope Proteins Viral Proteins A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1:1:1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes. © The Royal Society of Chemistry.2015. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1744683X_v11_n15_p3003_Vitiello http://hdl.handle.net/20.500.12110/paper_1744683X_v11_n15_p3003_Vitiello |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Association reactions Cell membranes Cholesterol Cytology Dynamic light scattering Electron spin resonance spectroscopy Glycoproteins Light scattering Magnetic moments Molecular dynamics Peptides Phospholipids Spin dynamics Viruses Asymmetric perturbations Comparative analysis Herpes simplex virus Molecular dynamics simulations Molecular mechanism Neutron reflectivity Phosphatidylcholine Specific interaction Lipid bilayers Simplexvirus 1-palmitoyl-2-oleoylphosphatidylcholine cholesterol gH625 peptide, Herpes simplex virus type I glycoprotein lipid bilayer peptide phosphatidylcholine sphingomyelin virus envelope protein virus protein chemistry lipid bilayer molecular dynamics protein tertiary structure Cholesterol Glycoproteins Lipid Bilayers Molecular Dynamics Simulation Peptides Phosphatidylcholines Protein Structure, Tertiary Sphingomyelins Viral Envelope Proteins Viral Proteins |
| spellingShingle |
Association reactions Cell membranes Cholesterol Cytology Dynamic light scattering Electron spin resonance spectroscopy Glycoproteins Light scattering Magnetic moments Molecular dynamics Peptides Phospholipids Spin dynamics Viruses Asymmetric perturbations Comparative analysis Herpes simplex virus Molecular dynamics simulations Molecular mechanism Neutron reflectivity Phosphatidylcholine Specific interaction Lipid bilayers Simplexvirus 1-palmitoyl-2-oleoylphosphatidylcholine cholesterol gH625 peptide, Herpes simplex virus type I glycoprotein lipid bilayer peptide phosphatidylcholine sphingomyelin virus envelope protein virus protein chemistry lipid bilayer molecular dynamics protein tertiary structure Cholesterol Glycoproteins Lipid Bilayers Molecular Dynamics Simulation Peptides Phosphatidylcholines Protein Structure, Tertiary Sphingomyelins Viral Envelope Proteins Viral Proteins Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| topic_facet |
Association reactions Cell membranes Cholesterol Cytology Dynamic light scattering Electron spin resonance spectroscopy Glycoproteins Light scattering Magnetic moments Molecular dynamics Peptides Phospholipids Spin dynamics Viruses Asymmetric perturbations Comparative analysis Herpes simplex virus Molecular dynamics simulations Molecular mechanism Neutron reflectivity Phosphatidylcholine Specific interaction Lipid bilayers Simplexvirus 1-palmitoyl-2-oleoylphosphatidylcholine cholesterol gH625 peptide, Herpes simplex virus type I glycoprotein lipid bilayer peptide phosphatidylcholine sphingomyelin virus envelope protein virus protein chemistry lipid bilayer molecular dynamics protein tertiary structure Cholesterol Glycoproteins Lipid Bilayers Molecular Dynamics Simulation Peptides Phosphatidylcholines Protein Structure, Tertiary Sphingomyelins Viral Envelope Proteins Viral Proteins |
| description |
A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1:1:1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes. © The Royal Society of Chemistry.2015. |
| title |
Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| title_short |
Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| title_full |
Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| title_fullStr |
Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| title_full_unstemmed |
Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type i glycoprotein gH occurs through a cholesterol-dependent mechanism |
| title_sort |
fusion of raft-like lipid bilayers operated by a membranotropic domain of the hsv-type i glycoprotein gh occurs through a cholesterol-dependent mechanism |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1744683X_v11_n15_p3003_Vitiello http://hdl.handle.net/20.500.12110/paper_1744683X_v11_n15_p3003_Vitiello |
| _version_ |
1768544750034485248 |