Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , |
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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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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799134634698604544 |