2K8J
Solution structure of HCV p7 tm2
Summary for 2K8J
| Entry DOI | 10.2210/pdb2k8j/pdb |
| NMR Information | BMRB: 15951 |
| Descriptor | p7tm2 (1 entity in total) |
| Functional Keywords | p7 polypeptide, hcv, ion chaneling, transmembrane, viral protein |
| Cellular location | Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein. RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26662 |
| Total number of polymer chains | 1 |
| Total formula weight | 3153.85 |
| Authors | Montserret, R.,Penin, F. (deposition date: 2008-09-12, release date: 2009-01-13, Last modification date: 2024-05-01) |
| Primary citation | Montserret, R.,Saint, N.,Vanbelle, C.,Salvay, A.G.,Simorre, J.P.,Ebel, C.,Sapay, N.,Renisio, J.G.,Bockmann, A.,Steinmann, E.,Pietschmann, T.,Dubuisson, J.,Chipot, C.,Penin, F. NMR structure and ion channel activity of the p7 protein from hepatitis C virus. J.Biol.Chem., 285:31446-31461, 2010 Cited by PubMed Abstract: The small membrane protein p7 of hepatitis C virus forms oligomers and exhibits ion channel activity essential for virus infectivity. These viroporin features render p7 an attractive target for antiviral drug development. In this study, p7 from strain HCV-J (genotype 1b) was chemically synthesized and purified for ion channel activity measurements and structure analyses. p7 forms cation-selective ion channels in planar lipid bilayers and at the single-channel level by the patch clamp technique. Ion channel activity was shown to be inhibited by hexamethylene amiloride but not by amantadine. Circular dichroism analyses revealed that the structure of p7 is mainly α-helical, irrespective of the membrane mimetic medium (e.g. lysolipids, detergents, or organic solvent/water mixtures). The secondary structure elements of the monomeric form of p7 were determined by (1)H and (13)C NMR in trifluoroethanol/water mixtures. Molecular dynamics simulations in a model membrane were combined synergistically with structural data obtained from NMR experiments. This approach allowed us to determine the secondary structure elements of p7, which significantly differ from predictions, and to propose a three-dimensional model of the monomeric form of p7 associated with the phospholipid bilayer. These studies revealed the presence of a turn connecting an unexpected N-terminal α-helix to the first transmembrane helix, TM1, and a long cytosolic loop bearing the dibasic motif and connecting TM1 to TM2. These results provide the first detailed experimental structural framework for a better understanding of p7 processing, oligomerization, and ion channel gating mechanism. PubMed: 20667830DOI: 10.1074/jbc.M110.122895 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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