Cargando…

Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration

To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in gian...

Descripción completa

Detalles Bibliográficos
Autores principales: Rice, Amy, Haldar, Sourav, Wang, Eric, Blank, Paul S., Akimov, Sergey A., Galimzyanov, Timur R., Pastor, Richard W., Zimmerberg, Joshua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722698/
https://www.ncbi.nlm.nih.gov/pubmed/36470871
http://dx.doi.org/10.1038/s41467-022-34576-z
_version_ 1784844010813128704
author Rice, Amy
Haldar, Sourav
Wang, Eric
Blank, Paul S.
Akimov, Sergey A.
Galimzyanov, Timur R.
Pastor, Richard W.
Zimmerberg, Joshua
author_facet Rice, Amy
Haldar, Sourav
Wang, Eric
Blank, Paul S.
Akimov, Sergey A.
Galimzyanov, Timur R.
Pastor, Richard W.
Zimmerberg, Joshua
author_sort Rice, Amy
collection PubMed
description To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus’ hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FPs are heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FPs in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain forms with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FPs thins the membrane as above, and the FPs of that dimer tilt, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid.
format Online
Article
Text
id pubmed-9722698
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-97226982022-12-07 Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration Rice, Amy Haldar, Sourav Wang, Eric Blank, Paul S. Akimov, Sergey A. Galimzyanov, Timur R. Pastor, Richard W. Zimmerberg, Joshua Nat Commun Article To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus’ hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FPs are heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FPs in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain forms with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FPs thins the membrane as above, and the FPs of that dimer tilt, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid. Nature Publishing Group UK 2022-12-05 /pmc/articles/PMC9722698/ /pubmed/36470871 http://dx.doi.org/10.1038/s41467-022-34576-z Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rice, Amy
Haldar, Sourav
Wang, Eric
Blank, Paul S.
Akimov, Sergey A.
Galimzyanov, Timur R.
Pastor, Richard W.
Zimmerberg, Joshua
Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title_full Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title_fullStr Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title_full_unstemmed Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title_short Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
title_sort planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722698/
https://www.ncbi.nlm.nih.gov/pubmed/36470871
http://dx.doi.org/10.1038/s41467-022-34576-z
work_keys_str_mv AT riceamy planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT haldarsourav planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT wangeric planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT blankpauls planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT akimovsergeya planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT galimzyanovtimurr planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT pastorrichardw planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation
AT zimmerbergjoshua planaraggregationoftheinfluenzaviralfusionpeptidealtersmembranestructureandhydrationpromotingporation