PMID- 17507273
OWN - NLM
STAT- MEDLINE
DCOM- 20071217
LR  - 20101118
IS  - 1093-3263 (Print)
IS  - 1093-3263 (Linking)
VI  - 26
IP  - 2
DP  - 2007 Sep
TI  - Structural and functional comparison of the non-structural protein 4B in 
      flaviviridae.
PG  - 546-57
AB  - Flaviviridae are evolutionarily related viruses, comprising the hepatitis C virus 
      (HCV), with the non-structural protein 4B (NS4B) as one of the least 
      characterized proteins. NS4B is located in the endoplasmic reticulum membrane and 
      is assumed to be a multifunctional protein. However, detailed structure 
      information is missing. The hydrophobic nature of NS4B is a major difficulty for 
      many experimental techniques. We applied bioinformatics methods to analyse 
      structural and functional properties of NS4B in different viruses. We distinguish 
      a central non-globular membrane portion with four to five transmembrane regions 
      from an N- and C-terminal part with non-transmembrane helical elements. We 
      demonstrate high similarity in sequence and structure for the C-terminal part 
      within the flaviviridae family. A palmitoylation site contained in the C-terminal 
      part of HCV is equally conserved in GB virus B. Furthermore, we identify and 
      characterize an N-terminal basic leucine zipper (bZIP) motif in HCV, which is 
      suggestive of a functionally important interaction site. In addition, we model 
      the interaction of the bZIP region with the recently identified interaction 
      partner CREB-RP/ATF6beta, a human activating transcription factor involved in 
      ER-stress. In conclusion, the versatile structure, together with functional sites 
      and motifs, possibly enables NS4B to adopt a role as protein hub in the 
      membranous web interaction network of virus and host proteins. Important 
      structural and functional properties of NS4B are predicted with implications for 
      ER-stress response, altered gene expression and replication efficacy.
FAU - Welsch, Christoph
AU  - Welsch C
AD  - Internal Medicine II, Saarland University Hospital, Kirrberger Strasse, 66421 
      Homburg/Saar, Germany. christoph.welsch@uniklinikum-saarland.de
FAU - Albrecht, Mario
AU  - Albrecht M
FAU - Maydt, Jochen
AU  - Maydt J
FAU - Herrmann, Eva
AU  - Herrmann E
FAU - Welker, Martin Walter
AU  - Welker MW
FAU - Sarrazin, Christoph
AU  - Sarrazin C
FAU - Scheidig, Axel
AU  - Scheidig A
FAU - Lengauer, Thomas
AU  - Lengauer T
FAU - Zeuzem, Stefan
AU  - Zeuzem S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070404
PL  - United States
TA  - J Mol Graph Model
JT  - Journal of molecular graphics & modelling
JID - 9716237
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Computer Simulation
MH  - Endoplasmic Reticulum/metabolism
MH  - Flaviviridae/*metabolism
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Viral Nonstructural Proteins/*chemistry/genetics/*metabolism
EDAT- 2007/05/18 09:00
MHDA- 2007/12/18 09:00
CRDT- 2007/05/18 09:00
PHST- 2006/10/06 00:00 [received]
PHST- 2007/03/23 00:00 [revised]
PHST- 2007/03/28 00:00 [accepted]
PHST- 2007/05/18 09:00 [pubmed]
PHST- 2007/12/18 09:00 [medline]
PHST- 2007/05/18 09:00 [entrez]
AID - S1093-3263(07)00067-8 [pii]
AID - 10.1016/j.jmgm.2007.03.012 [doi]
PST - ppublish
SO  - J Mol Graph Model. 2007 Sep;26(2):546-57. doi: 10.1016/j.jmgm.2007.03.012. Epub 
      2007 Apr 4.