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Transient Excursions to Membrane Core as Determinants of Influenza Virus Fusion Peptide Activity

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cris.lastimport.scopus2024-02-12T19:39:00Z
dc.abstract.enFusion of viral and host cell membranes is a critical step in the life cycle of enveloped viruses. In the case of influenza virus, it is mediated by subunit 2 of hemagglutinin (HA) glycoprotein whose N-terminal fragments insert into the target membrane and initiate lipid exchange. These isolated fragments, known as fusion peptides (HAfp), already possess own fusogenic activity towards liposomes. Although they have long been studied with the hope to uncover the details of HA-mediated fusion, their actual mechanism of action remains elusive. Here, we use extensive molecular dynamics simulations combined with experimental studies of three HAfp variants to fully characterize their free energy landscape and interaction with lipid bilayer. In addition to customary assumed peptides localization at lipid–water interface, we characterize membrane-spanning configurations, which turn out to be metastable for active HAfps and unstable for the fusion inactive W14A mutant. We show that, while the degree of membrane perturbation by surface peptide configurations is relatively low and does not show any mutation-related differences, the effect of deeply inserted configurations is significant and correlates with insertion depth of the N-terminal amino group which is the highest for the wild type HAfp. Finally, we demonstrate the feasibility of spontaneous peptide transition to intramembrane location and the critical role of strictly conserved tryptofan residue 14 in this process.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorDudek, Anita
dc.contributor.authorBorkowska, Paulina
dc.contributor.authorSetny, Piotr
dc.contributor.authorWorch, Remigiusz
dc.date.accessioned2024-01-26T11:05:13Z
dc.date.available2024-01-26T11:05:13Z
dc.date.copyright2021-05-18
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financeŚrodki finansowe przyznane na realizację projektu w zakresie badań naukowych lub prac rozwojowych
dc.description.number10
dc.description.versionFINAL_PUBLISHED
dc.description.volume22
dc.identifier.doi10.3390/IJMS22105301
dc.identifier.issn1422-0067
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/123707
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/22/10/5301/pdf
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pages5301-1-20
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.eninfluenza virus fusion peptides
dc.subject.enpeptide-membrane interactions
dc.subject.enmembrane fusion
dc.titleTransient Excursions to Membrane Core as Determinants of Influenza Virus Fusion Peptide Activity
dc.typeJournalArticle
dspace.entity.typePublication