TY  - THES
T1  - Molecular modeling of the transmembrane domain of envelope glycoproteins from flaviviridae viruses
A1  - Jusoh,Siti Azma
Y1  - 2010/12/22
N2  - The putative transmembrane (TM) domains of the envelope glycoproteins from the family Flaviviridae consist of a highly polar segment in between two hydrophobic stretches. This type of sequence pattern does not yet exist in the database of high resolution structures of membrane proteins. Mutagenesis studies have shown that the TM domains act as membrane and signal anchors, and are responsible for heterodimerization. In hepatitis C virus (HCV), the TM domains of the envelope glycoproteins E1 and E2 were hypothesized to heterodimerize via an ion pair of Lys-Asp. Our MD simulations showed that the E1-E2 heterodimer formed by the charged residues located in the core of the lipid bilayer stabilized the helical conformation of E2. We compared the effect of other types of ion pair interactions using engineered peptides and obtained similar results. We found that an Asp amino acid had the strongest kink-inducing effect on the helix when it was located in the middle of a single-pass TM helix. The extended analyses on dengue, Japanese encephalitis, West Nile and bovine viral diarrhea viruses again showed that their putative TM domains behave similarly. All the TM domains of the E1/prM tended to tilt and remain helical in membrane bilayer. In contrast, the TM domains of the E2/E that contain a central Asp residue were severely kinked. Altogether, these TM domains illustrated a similar structural behavior in the lipid bilayer milieu.
KW  - Membranproteine
KW  - Ionenpaar
KW  - Molekulardynamik
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2010/3489
ER  -