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Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment

2020Journal article Open access
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dc.contributor.authorLousa, Diana
dc.contributor.authorPinto, Antónia R. T.
dc.contributor.authorCampos, Sara R. R.
dc.contributor.authorBaptista, António M.
dc.contributor.authorVeiga, Ana Salomé
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorSoares, Cláudio M.
dc.date.accessioned2021-04-07T11:18:22Z
dc.date.available2021-04-07T11:18:22Z
dc.date.issued2020
dc.description© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractThe influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the host endosome. However, the mechanism by which pH modulates the molecular properties of the fusion peptide remains unclear. To answer this question, we performed the first constant-pH molecular dynamics simulations of the influenza fusion peptide in a membrane, extending for 40 µs of aggregated time. The simulations were combined with spectroscopic data, which showed that the peptide is twofold more active in promoting lipid mixing of model membranes at pH 5 than at pH 7.4. The realistic treatment of protonation introduced by the constant-pH molecular dynamics simulations revealed that low pH stabilizes a vertical membrane-spanning conformation and leads to more frequent contacts between the fusion peptide and the lipid headgroups, which may explain the increase in activity. The study also revealed that the N-terminal region is determinant for the peptide's effect on the membrane.pt_PT
dc.description.sponsorshipThis work was financially supported by FCT—Fundação para a Ciência e a Tecnologia, Portugal, through projects PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011. 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) and by national funds through FCT—Fundação para a Ciência e a Tecnologia. DL was supported by FCT post-doc fellowship SFRH/BPD/92537/2013.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSci Rep. 2020 Nov 18;10(1):20082pt_PT
dc.identifier.doi10.1038/s41598-020-77040-ypt_PT
dc.identifier.eissn2045-2322
dc.identifier.urihttp://hdl.handle.net/10451/47270
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationLISBOA-01-0145-FEDER-007660pt_PT
dc.relationMembrane fusion mechanism of Influenza Hemagglutinin: a simulation and biophysical approach.
dc.relationUsing computational and experimental methods to provide a global characterization of viral fusion peptides
dc.relationStrategic Project - LA 4 - 2011-2012
dc.relation.publisherversionhttps://www.nature.com/srep/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleEffect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experimentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMembrane fusion mechanism of Influenza Hemagglutinin: a simulation and biophysical approach.
oaire.awardTitleUsing computational and experimental methods to provide a global characterization of viral fusion peptides
oaire.awardTitleStrategic Project - LA 4 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-BIQ%2F114774%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCCI-BIO%2F28200%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FEQB%2FLA0004%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F92537%2F2013/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage20082pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamSFRH
person.familyNameVeiga
person.familyNameCastanho
person.givenNameAna Salome
person.givenNameMiguel
person.identifier.orcid0000-0002-9892-2243
person.identifier.orcid0000-0001-7891-7562
person.identifier.scopus-author-id56745037100
person.identifier.scopus-author-id56605575600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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