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Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle

The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of doma...

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Autores principales: Ashworth Briggs, Esther L., Gomes, Rafael G.B., Elhussein, Malaz, Collier, William, Stuart Findlow, I., Khalid, Syma, McCormick, Chris J., Williamson, Philip T.F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Pub. Co 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768108/
https://www.ncbi.nlm.nih.gov/pubmed/25944559
http://dx.doi.org/10.1016/j.bbamem.2015.04.015
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author Ashworth Briggs, Esther L.
Gomes, Rafael G.B.
Elhussein, Malaz
Collier, William
Stuart Findlow, I.
Khalid, Syma
McCormick, Chris J.
Williamson, Philip T.F.
author_facet Ashworth Briggs, Esther L.
Gomes, Rafael G.B.
Elhussein, Malaz
Collier, William
Stuart Findlow, I.
Khalid, Syma
McCormick, Chris J.
Williamson, Philip T.F.
author_sort Ashworth Briggs, Esther L.
collection PubMed
description The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions.
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spelling pubmed-47681082016-02-29 Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle Ashworth Briggs, Esther L. Gomes, Rafael G.B. Elhussein, Malaz Collier, William Stuart Findlow, I. Khalid, Syma McCormick, Chris J. Williamson, Philip T.F. Biochim Biophys Acta Article The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions. Elsevier Pub. Co 2015-08 /pmc/articles/PMC4768108/ /pubmed/25944559 http://dx.doi.org/10.1016/j.bbamem.2015.04.015 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ashworth Briggs, Esther L.
Gomes, Rafael G.B.
Elhussein, Malaz
Collier, William
Stuart Findlow, I.
Khalid, Syma
McCormick, Chris J.
Williamson, Philip T.F.
Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title_full Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title_fullStr Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title_full_unstemmed Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title_short Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle
title_sort interaction between the ns4b amphipathic helix, ah2, and charged lipid headgroups alters membrane morphology and ah2 oligomeric state — implications for the hepatitis c virus life cycle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768108/
https://www.ncbi.nlm.nih.gov/pubmed/25944559
http://dx.doi.org/10.1016/j.bbamem.2015.04.015
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