PMID- 25944559
OWN - NLM
STAT- MEDLINE
DCOM- 20150901
LR  - 20181113
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1848
IP  - 8
DP  - 2015 Aug
TI  - 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.
PG  - 1671-7
LID - S0005-2736(15)00138-8 [pii]
LID - 10.1016/j.bbamem.2015.04.015 [doi]
AB  - 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.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Ashworth Briggs, Esther L
AU  - Ashworth Briggs EL
AD  - Centre for Biological Sciences/Institute for Life Sciences, University of 
      Southampton, Highfield Campus, Southampton SO17 1BJ, UK.
FAU - Gomes, Rafael G B
AU  - Gomes RG
AD  - Centre for Biological Sciences/Institute for Life Sciences, University of 
      Southampton, Highfield Campus, Southampton SO17 1BJ, UK; School of Medicine, 
      University of Southampton, Southampton SO16 6YD, UK.
FAU - Elhussein, Malaz
AU  - Elhussein M
AD  - School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
FAU - Collier, William
AU  - Collier W
AD  - Centre for Biological Sciences/Institute for Life Sciences, University of 
      Southampton, Highfield Campus, Southampton SO17 1BJ, UK.
FAU - Findlow, I Stuart
AU  - Findlow IS
AD  - Centre for Biological Sciences/Institute for Life Sciences, University of 
      Southampton, Highfield Campus, Southampton SO17 1BJ, UK.
FAU - Khalid, Syma
AU  - Khalid S
AD  - School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
FAU - McCormick, Chris J
AU  - McCormick CJ
AD  - School of Medicine, University of Southampton, Southampton SO16 6YD, UK. 
      Electronic address: C.J.McCormick@soton.ac.uk.
FAU - Williamson, Philip T F
AU  - Williamson PT
AD  - Centre for Biological Sciences/Institute for Life Sciences, University of 
      Southampton, Highfield Campus, Southampton SO17 1BJ, UK. Electronic address: 
      P.T.Williamson@soton.ac.uk.
LA  - eng
GR  - 090658/z/09/z/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150502
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Lipid Bilayers)
RN  - 0 (Membrane Lipids)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Cell Membrane/*metabolism
MH  - Hepacivirus/growth & development/*metabolism
MH  - Lipid Bilayers
MH  - Membrane Lipids/chemistry/*metabolism
MH  - Molecular Dynamics Simulation
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Conformation
MH  - Protein Multimerization
MH  - Structure-Activity Relationship
MH  - Surface Properties
MH  - Viral Nonstructural Proteins/chemistry/*metabolism
MH  - *Virus Replication
PMC - PMC4768108
OTO - NOTNLM
OT  - Hepatitis C Virus
OT  - Membrane biophysics
OT  - Membrane remodelling
OT  - Molecular dynamics
OT  - Solid-state NMR
EDAT- 2015/05/07 06:00
MHDA- 2015/09/02 06:00
PMCR- 2015/08/01
CRDT- 2015/05/07 06:00
PHST- 2014/10/07 00:00 [received]
PHST- 2015/02/27 00:00 [revised]
PHST- 2015/04/25 00:00 [accepted]
PHST- 2015/05/07 06:00 [entrez]
PHST- 2015/05/07 06:00 [pubmed]
PHST- 2015/09/02 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - S0005-2736(15)00138-8 [pii]
AID - 10.1016/j.bbamem.2015.04.015 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2015 Aug;1848(8):1671-7. doi: 10.1016/j.bbamem.2015.04.015. 
      Epub 2015 May 2.