期刊
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
卷 39, 期 7, 页码 1097-1104出版社
SPRINGER
DOI: 10.1007/s00249-009-0533-y
关键词
Hepatitis C virus; p7; Solid-state NMR; Bicelles
类别
资金
- NIBIB NIH HHS [P41 EB002031, P41EB002031] Funding Source: Medline
- NIDDK NIH HHS [T32DK00723332] Funding Source: Medline
- NIGMS NIH HHS [R01 GM066978, R01 GM075877] Funding Source: Medline
The p7 protein of hepatitis C virus (HCV) plays an important role in the viral lifecycle. Like other members of the viroporin family of small membrane proteins, the amino acid sequence of p7 is largely conserved over the entire range of genotypes, and it forms ion channels that can be blocked by a number of established channel-blocking compounds. Its characteristics as a membrane protein make it difficult to study by most structural techniques, since it requires the presence of lipids to fold and function properly. Purified p7 can be incorporated into phospholipid bilayers and micelles. Initial solid-state nuclear magnetic resonance (NMR) studies of p7 in 14-O-PC/6-O-PC bicelles indicate that the protein contains helical segments that are tilted approximately 10A degrees and 25A degrees relative to the bilayer normal. A truncated construct corresponding to the second transmembrane domain of p7 is shown to have properties similar to those of the full-length protein, and was used to determine that the helix segment tilted at 10A degrees is in the C-terminal portion of the protein. The addition of the channel blocker amantadine to the full-length protein resulted in selective chemical shift changes, demonstrating that NMR has a potential role in the development of drugs targeted to p7.
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