Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures

Detalhes bibliográficos
Autor(a) principal: Valério, Mariana
Data de Publicação: 2022
Outros Autores: Mendonça, Diogo A., Morais, João, Buga, Carolina C., Cruz, Carlos H., Castanho, Miguel A. R. B., Melo, Manuel N., Soares, Cláudio M., Veiga, Ana Salomé, Lousa, Diana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/57580
Resumo: © 2022 The Authors. Published by American Chemical Society
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spelling Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures© 2022 The Authors. Published by American Chemical SocietyParamyxoviruses are enveloped viruses harboring a negative-sense RNA genome that must enter the host’s cells to replicate. In the case of the parainfluenza virus, the cell entry process starts with the recognition and attachment to target receptors, followed by proteolytic cleavage of the fusion glycoprotein (F) protein, exposing the fusion peptide (FP) region. The FP is responsible for binding to the target membrane, and it is believed to play a crucial role in the fusion process, but the mechanism by which the parainfluenza FP (PIFP) promotes membrane fusion is still unclear. To elucidate this matter, we performed biophysical experimentation of the PIFP in membranes, together with coarse grain (CG) and atomistic (AA) molecular dynamics (MD) simulations. The simulation results led to the pinpointing of the most important PIFP amino acid residues for membrane fusion and show that, at high concentrations, the peptide induces the formation of a water-permeable porelike structure. This structure promotes lipid head intrusion and lipid tail protrusion, which facilitates membrane fusion. Biophysical experimental results validate these findings, showing that, depending on the peptide/lipid ratio, the PIFP can promote fusion and/or membrane leakage. Our work furthers the understanding of the PIFP-induced membrane fusion process, which might help foster development in the field of viral entry inhibition.This work was financially supported by FCT-Fundação para a Ciência e a Tecnologia, Portugal, through project PTDC/CCI-BIO/28200/2017 and by the European Union (H2020-FETOPEN-2018-2019-2020-01, grant no. 828774). This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020_Programa Operacional Competitividade e Internacionalização (POCI). M.V. and D.A.M. thank FCT for their PhD fellowships (SFRH/BD/148542/2019 and PD/BD/136752/2018, respectively). M.N.M. thanks FCT for the Post-Doc fellowship CEECIND/04124/2017. M.N.M. and D.L. thank the MACC for the computing hours in their HPC center (CPCA/A0/7329/2020 and CPCA/A0/7305/2020).ACS PublicationsRepositório da Universidade de LisboaValério, MarianaMendonça, Diogo A.Morais, JoãoBuga, Carolina C.Cruz, Carlos H.Castanho, Miguel A. R. B.Melo, Manuel N.Soares, Cláudio M.Veiga, Ana SaloméLousa, Diana2023-05-24T14:32:37Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57580engACS Chem. Biol. 2022, 17, 7, 1831–18431554-892910.1021/acschembio.2c002081554-8937info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:06:09Zoai:repositorio.ul.pt:10451/57580Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:04.234159Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
title Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
spellingShingle Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
Valério, Mariana
title_short Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
title_full Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
title_fullStr Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
title_full_unstemmed Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
title_sort Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
author Valério, Mariana
author_facet Valério, Mariana
Mendonça, Diogo A.
Morais, João
Buga, Carolina C.
Cruz, Carlos H.
Castanho, Miguel A. R. B.
Melo, Manuel N.
Soares, Cláudio M.
Veiga, Ana Salomé
Lousa, Diana
author_role author
author2 Mendonça, Diogo A.
Morais, João
Buga, Carolina C.
Cruz, Carlos H.
Castanho, Miguel A. R. B.
Melo, Manuel N.
Soares, Cláudio M.
Veiga, Ana Salomé
Lousa, Diana
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Valério, Mariana
Mendonça, Diogo A.
Morais, João
Buga, Carolina C.
Cruz, Carlos H.
Castanho, Miguel A. R. B.
Melo, Manuel N.
Soares, Cláudio M.
Veiga, Ana Salomé
Lousa, Diana
description © 2022 The Authors. Published by American Chemical Society
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-01-01T00:00:00Z
2023-05-24T14:32:37Z
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://hdl.handle.net/10451/57580
url http://hdl.handle.net/10451/57580
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Chem. Biol. 2022, 17, 7, 1831–1843
1554-8929
10.1021/acschembio.2c00208
1554-8937
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv ACS Publications
publisher.none.fl_str_mv ACS Publications
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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