On the role of surrounding regions in the fusion peptide in dengue virus infection
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.virol.2021.02.012 http://hdl.handle.net/11449/207365 |
Resumo: | Dengue virus infection depends on its fusion with the host membrane, where the binding occurs through interaction between proteins on the virus cell surface and specific viral receptors on target membranes. This process is mediated by the fusion peptide located between residues 98 and 112 (DRGWGNGCGLFGKGG) that forms a loop in domain II of dengue E glycoprotein. In this study, we evaluated the role of fusion peptide surrounding regions (88–97 and 113–123) of the Dengue 2 subtype on its interaction with the membrane and fusion activity. These sequences are important to stabilize the fusion peptide loop and increase fusion activity. Three peptides, besides the fusion peptide, were synthesized by SPPS using the Fmoc chemical approach. The first contains the fusion peptide and the C-terminal region of the loop (sequence 98–123); another contains the N-terminal region (88–112) and the larger peptide contains both regions (88–123). The peptides were able to interact with a model membrane. Differences in morphology of the monolayer promoted by the peptides were assessed by Brewster Angle Microscopy (BAM). Our data indicated that the C-terminal region of fusion peptide loop is more efficient in promoting fusion and interacting with the membrane than the N-terminal sequence, which is responsible for the electrostatic initial interaction. We propose a 2-step mechanism for the interaction of the dengue virus fusion peptide with the host membrane, where the N-terminal sequence docks electrostatically on the headgroups and then the C-terminal interacts via hydrophobic forces in the acyl chains. |
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Repositório Institucional da UNESP |
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On the role of surrounding regions in the fusion peptide in dengue virus infectionBrewster angle microscopyDengueFlavivirusFusion peptideLangmuir monolayersPeptide synthesisDengue virus infection depends on its fusion with the host membrane, where the binding occurs through interaction between proteins on the virus cell surface and specific viral receptors on target membranes. This process is mediated by the fusion peptide located between residues 98 and 112 (DRGWGNGCGLFGKGG) that forms a loop in domain II of dengue E glycoprotein. In this study, we evaluated the role of fusion peptide surrounding regions (88–97 and 113–123) of the Dengue 2 subtype on its interaction with the membrane and fusion activity. These sequences are important to stabilize the fusion peptide loop and increase fusion activity. Three peptides, besides the fusion peptide, were synthesized by SPPS using the Fmoc chemical approach. The first contains the fusion peptide and the C-terminal region of the loop (sequence 98–123); another contains the N-terminal region (88–112) and the larger peptide contains both regions (88–123). The peptides were able to interact with a model membrane. Differences in morphology of the monolayer promoted by the peptides were assessed by Brewster Angle Microscopy (BAM). Our data indicated that the C-terminal region of fusion peptide loop is more efficient in promoting fusion and interacting with the membrane than the N-terminal sequence, which is responsible for the electrostatic initial interaction. We propose a 2-step mechanism for the interaction of the dengue virus fusion peptide with the host membrane, where the N-terminal sequence docks electrostatically on the headgroups and then the C-terminal interacts via hydrophobic forces in the acyl chains.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)EMCDepartamento de Bioquímica e Química Orgânica Instituto de Química UNESP -Univ Estadual PaulistaInstituto de Física de São Carlos Universidade de São Paulo USP, São CarlosDepartment of Chemistry The Ohio State UniversityDepartamento de Bioquímica e Química Orgânica Instituto de Química UNESP -Univ Estadual PaulistaUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)The Ohio State UniversityCespedes, Graziely F. [UNESP]Nobre, Thatyane M.Oliveira, Osvaldo N.Bong, DennisCilli, Eduardo M. [UNESP]2021-06-25T10:53:54Z2021-06-25T10:53:54Z2021-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article62-69http://dx.doi.org/10.1016/j.virol.2021.02.012Virology, v. 557, p. 62-69.1096-03410042-6822http://hdl.handle.net/11449/20736510.1016/j.virol.2021.02.0122-s2.0-85101735317Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengVirologyinfo:eu-repo/semantics/openAccess2021-10-22T18:27:14Zoai:repositorio.unesp.br:11449/207365Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-22T18:27:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
title |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
spellingShingle |
On the role of surrounding regions in the fusion peptide in dengue virus infection Cespedes, Graziely F. [UNESP] Brewster angle microscopy Dengue Flavivirus Fusion peptide Langmuir monolayers Peptide synthesis |
title_short |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
title_full |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
title_fullStr |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
title_full_unstemmed |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
title_sort |
On the role of surrounding regions in the fusion peptide in dengue virus infection |
author |
Cespedes, Graziely F. [UNESP] |
author_facet |
Cespedes, Graziely F. [UNESP] Nobre, Thatyane M. Oliveira, Osvaldo N. Bong, Dennis Cilli, Eduardo M. [UNESP] |
author_role |
author |
author2 |
Nobre, Thatyane M. Oliveira, Osvaldo N. Bong, Dennis Cilli, Eduardo M. [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) The Ohio State University |
dc.contributor.author.fl_str_mv |
Cespedes, Graziely F. [UNESP] Nobre, Thatyane M. Oliveira, Osvaldo N. Bong, Dennis Cilli, Eduardo M. [UNESP] |
dc.subject.por.fl_str_mv |
Brewster angle microscopy Dengue Flavivirus Fusion peptide Langmuir monolayers Peptide synthesis |
topic |
Brewster angle microscopy Dengue Flavivirus Fusion peptide Langmuir monolayers Peptide synthesis |
description |
Dengue virus infection depends on its fusion with the host membrane, where the binding occurs through interaction between proteins on the virus cell surface and specific viral receptors on target membranes. This process is mediated by the fusion peptide located between residues 98 and 112 (DRGWGNGCGLFGKGG) that forms a loop in domain II of dengue E glycoprotein. In this study, we evaluated the role of fusion peptide surrounding regions (88–97 and 113–123) of the Dengue 2 subtype on its interaction with the membrane and fusion activity. These sequences are important to stabilize the fusion peptide loop and increase fusion activity. Three peptides, besides the fusion peptide, were synthesized by SPPS using the Fmoc chemical approach. The first contains the fusion peptide and the C-terminal region of the loop (sequence 98–123); another contains the N-terminal region (88–112) and the larger peptide contains both regions (88–123). The peptides were able to interact with a model membrane. Differences in morphology of the monolayer promoted by the peptides were assessed by Brewster Angle Microscopy (BAM). Our data indicated that the C-terminal region of fusion peptide loop is more efficient in promoting fusion and interacting with the membrane than the N-terminal sequence, which is responsible for the electrostatic initial interaction. We propose a 2-step mechanism for the interaction of the dengue virus fusion peptide with the host membrane, where the N-terminal sequence docks electrostatically on the headgroups and then the C-terminal interacts via hydrophobic forces in the acyl chains. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T10:53:54Z 2021-06-25T10:53:54Z 2021-05-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.virol.2021.02.012 Virology, v. 557, p. 62-69. 1096-0341 0042-6822 http://hdl.handle.net/11449/207365 10.1016/j.virol.2021.02.012 2-s2.0-85101735317 |
url |
http://dx.doi.org/10.1016/j.virol.2021.02.012 http://hdl.handle.net/11449/207365 |
identifier_str_mv |
Virology, v. 557, p. 62-69. 1096-0341 0042-6822 10.1016/j.virol.2021.02.012 2-s2.0-85101735317 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Virology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
62-69 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1797789387541446656 |