Citation: Zhang Yuebin, Peng Xiangda, Ren Hong, Chu Huiying, Li Yan, Li Guohui. Cholesterol modulating the orientation of His17 in hepatitis C virus p7 (5a) viroporin-A molecular dynamic simulation study[J]. Chinese Chemical Letters, ;2018, 29(5): 719-723. doi: 10.1016/j.cclet.2017.09.053 shu

Cholesterol modulating the orientation of His17 in hepatitis C virus p7 (5a) viroporin-A molecular dynamic simulation study

Zhang Yuebin ^a,1 ,
Peng Xiangda ^a,1 ,
Ren Hong ^b,1 ,
Chu Huiying ^a ,
Li Yan ^a ,
Li Guohui ^a,,

a.
State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
b.
Aerospace Center Hospital, Beijing 100049, China

Corresponding author: Li Guohui, ghli@dicp.ac.cn

Received Date: 27 July 2017
Revised Date: 19 September 2017
Accepted Date: 22 September 2017
Available Online: 23 May 2017

Figures(4)

Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression of viral infection and the sensitivity of this channel to small-molecule inhibitors renders p7 a potential target for novel therapies against HCV infection. Previous biochemical experiments suggested that the His17 of p7 is a pore-lining residue and solvated-exposed to participate in channel gating. However, a recent NMR structural identification of the p7 hexamer in dodecylphosphocholine (DPC) micelles indicated that the His17 is embedded into the protein matrix. In this work, we performed molecular dynamic simulations to bridge the controversial observations. Our results illustrated that by incorporating the cholesterol into DOPC membranes to mimic an actual membrane-like composition, the orientation of His17 in the hexameric bundles spontaneously access to the central pore region, indicating a versatile property of the p7 viroporin conformation that could be voluntarily influenced by its surrounding environments.
- Hepatitis C virus,
- p7 Viroporin,
- Cholesterol,
- Molecular dynamic simulation,
- Conformational transition
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