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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Pub. Co
2015
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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. |
format | Online Article Text |
id | pubmed-4768108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Pub. Co |
record_format | MEDLINE/PubMed |
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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