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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

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
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 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.
hepatitis C virus, membrane remodelling, solid-state NMR, membrane biophysics, molecular dynamics
0304-4165
1671-1677
Ashworth Briggs, Esther L.
39dd3a37-e129-4934-af59-62f1cc15ca31
Gomes, Rafael G.B.
89b428e0-c16e-4a34-9ba2-69ace35865a1
Elhussein, Malaz
70264e9a-dbc9-40d1-8abd-64a3594d2815
Collier, William
c6583957-3a33-41be-bd3a-4db4a018a990
Stuart Findlow, I.
04a69f54-a99b-46a6-8955-ccdbf88763af
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
McCormick, Chris J.
0fce14bf-2f67-4d08-991f-114dd1e7f0bd
Williamson, Philip T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Ashworth Briggs, Esther L.
39dd3a37-e129-4934-af59-62f1cc15ca31
Gomes, Rafael G.B.
89b428e0-c16e-4a34-9ba2-69ace35865a1
Elhussein, Malaz
70264e9a-dbc9-40d1-8abd-64a3594d2815
Collier, William
c6583957-3a33-41be-bd3a-4db4a018a990
Stuart Findlow, I.
04a69f54-a99b-46a6-8955-ccdbf88763af
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
McCormick, Chris J.
0fce14bf-2f67-4d08-991f-114dd1e7f0bd
Williamson, Philip T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a

Ashworth Briggs, Esther L., Gomes, Rafael G.B., Elhussein, Malaz, Collier, William, Stuart Findlow, I., Khalid, Syma, McCormick, Chris J. and Williamson, Philip T.F. (2015) 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. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1848 (8), 1671-1677. (doi:10.1016/j.bbamem.2015.04.015).

Record type: Article

Abstract

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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More information

Accepted/In Press date: 25 April 2015
e-pub ahead of print date: 2 May 2015
Published date: 2015
Keywords: hepatitis C virus, membrane remodelling, solid-state NMR, membrane biophysics, molecular dynamics
Organisations: Chemistry, Molecular and Cellular, Faculty of Medicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 377188
URI: https://eprints.soton.ac.uk/id/eprint/377188
ISSN: 0304-4165
PURE UUID: 70c8c970-6291-4f74-b8da-5b189ec8c9ef
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044
ORCID for Philip T.F. Williamson: ORCID iD orcid.org/0000-0002-0231-8640

Catalogue record

Date deposited: 02 Jun 2015 12:39
Last modified: 14 Jul 2018 00:32

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