PMID- 17030859
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20220110
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 87
IP  - Pt 11
DP  - 2006 Nov
TI  - Dual topology of the processed hepatitis C virus protein NS4B is influenced by 
      the NS5A protein.
PG  - 3263-3272
LID - 10.1099/vir.0.82211-0 [doi]
AB  - Among the least-known hepatitis C virus proteins is the non-structural protein 4B 
      (NS4B). It localizes to the endoplasmic reticulum (ER) membrane and induces 
      membrane changes, resulting in a membranous web that is reported to be the locale 
      for virus replication. A model was presented previously for the topology of 
      recombinant HCV NS4B of the 1a genotype based on in vitro data. In this model, 
      the N-terminal tail of a considerable fraction of the NS4B molecules was 
      translocated into the ER lumen via a post-translational process, giving the 
      protein a dual transmembrane topology. It is now reported that translocation of 
      the N terminus also occurs for processed NS4B expressed in cells in the context 
      of the polyprotein. In the presence of NS5A, however, a lower degree of 
      translocation was observed, which may indicate that NS5A influences the topology 
      of NS4B. In vitro expression studies of NS4B from all major genotypes 
      demonstrated that translocation of the N terminus to the ER lumen is conserved 
      across genotypes. This clearly suggests an important function for this feature. 
      Furthermore, when disrupting a previously reported amphipathic helix (AH) in the 
      N terminus of NS4B, translocation was inhibited. As a disrupted AH also abolished 
      the ability of NS4B to rearrange membranes, these data indicate for the first 
      time an association between translocation of the N terminus and membrane 
      rearrangement. Finally, the present experiments also confirm the predicted 
      location of the first luminal loop to be around aa 112.
FAU - Lundin, Marika
AU  - Lundin M
AD  - Karolinska Institutet, Department of Medicine at Center for Molecular Medicine 
      (L8 : 01), Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.
FAU - Lindstrom, Hannah
AU  - Lindstrom H
AD  - Karolinska Institutet, Department of Medicine at Center for Molecular Medicine 
      (L8 : 01), Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.
FAU - Gronwall, Caroline
AU  - Gronwall C
AD  - The Royal Institute of Technology, Department of Biotechnology, Alba Nova 
      University Centre, Stockholm, Sweden.
FAU - Persson, Mats A A
AU  - Persson MAA
AD  - Karolinska Institutet, Department of Medicine at Center for Molecular Medicine 
      (L8 : 01), Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.
LA  - eng
SI  - GENBANK/AM113975
SI  - GENBANK/AM113976
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (NS4 protein, hepatitis C virus)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 2.7.7.48 (NS-5 protein, hepatitis C virus)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Endoplasmic Reticulum/metabolism
MH  - Glycosylation
MH  - Hepacivirus/metabolism/*physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Viral Nonstructural Proteins/chemistry/*metabolism/*physiology
EDAT- 2006/10/13 09:00
MHDA- 2006/11/15 09:00
CRDT- 2006/10/13 09:00
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
AID - 10.1099/vir.0.82211-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2006 Nov;87(Pt 11):3263-3272. doi: 10.1099/vir.0.82211-0.