76
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I
23-POS
Board 23
Structural Analysis of Putative HCV Glycoprotein E2 Binding Sites on Human CD81 in
Compared with Their Mouse Counterparts
Chun-Chun Chang
1,2
, Hao-Jen Hsu
3
, Je-Wen Liou
1
.
1
Department of Medical Sciences, Tzu Chi University, Hualien City, Taiwan,
2
Departments of
Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan,
3
Department of
Life Sciences, Tzu Chi University, Hualien City, Taiwan.
Hepatitis C virus (HCV), formally identified in 1989, is an enveloped virus with a single positive
stranded genomic RNA. HCV infection in patients often results in chronic hepatitis, liver
cirrhosis, and hepatocellular carcinoma. However, the treatments for HVC infection are still
limited. This might be due to the fact that the current cell and animal model systems are not
sufficient for studying the HCV infection in details.
In this study, we are firstly aiming to investigate the interactions between HCV E2 protein and
CD81 of host cells, which have been proved crucial for HCV entry into host cells, using
molecular docking. From the bioinformatic results, we should be able to develop the potential
peptide drugs for interrupting HCV E2/CD81 interactions to prevent the HCV infection into host
cells. Previous studies showed that HCV can bind to human CD81 with high specificity. For
comparison, homology modeling was also performed to obtain the structure of mouse CD81
using human CD81 as a template with high similarity up to 93%. So far, the docking results
showed that the short helices near C-terminal domain of HCV E2 bind to the head regions of
dimeric human CD81 with hydrophobic contacts, while the binding sites are altered when the
HCV E2 are docked to mouse CD81. Two peptides were designed based on the docking
prediction and the work were followed by the synthesis of fluorescent dye 5-carboxyfluorescein
labelled peptides and flow cytometry in order to measure the binding efficiency of the synthetic
peptides onto host cells.
