Chew Chee Foong, Vijayan Ranjit, Chang Jason, Zitzmann Nicole, Biggin Philip C
Biophys J. 2009 Jan;96(2):L10-2. doi: 10.1016/j.bpj.2008.10.004.
The p7 protein from hepatitis C virus is critical for the assembly and secretion of infectious virus, making it an attractive drug target. It is thought to be a viroporin with a demonstrated ion channel activity when reconstituted into planar lipid bilayers. Electron microscopy experiments suggest that p7 oligomers coexist as hexamers and heptamers. Proposed models of p7 oligomers assume the N-terminal helix to be the pore lining helix. Here, we demonstrate, via electrophysiology, that Cu(2+) has an inhibitory effect on the p7 ion channel and that the amino acid responsible for this inhibition is one histidine in each monomer. This information coupled with the p7 sequence data suggests that the N-terminal helix of p7 does indeed form the transmembrane pore and that this histidine is pore-lining. The information will aid in the construction of oligomeric pore-models and the interpretation of electron microscopy data.
丙型肝炎病毒的p7蛋白对于传染性病毒的组装和分泌至关重要，使其成为一个有吸引力的药物靶点。它被认为是一种病毒离子通道蛋白，在重组到平面脂质双分子层时具有已证实的离子通道活性。电子显微镜实验表明，p7寡聚体以六聚体和七聚体的形式共存。提出的p7寡聚体模型假定N端螺旋为孔衬螺旋。在这里，我们通过电生理学证明，Cu(2+) 对p7离子通道有抑制作用，并且负责这种抑制作用的氨基酸是每个单体中的一个组氨酸。这些信息与p7序列数据相结合表明，p7的N端螺旋确实形成跨膜孔，并且这个组氨酸是孔衬。这些信息将有助于构建寡聚体孔模型和解释电子显微镜数据。
