ArticleThe Journal of biological chemistry2010
NMR structure and ion channel activity of the p7 protein from hepatitis C virus.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 136 citations in OpenAlex.
- Enterovirus 2B protein: From viroporin to membrane stress sensor, mechanistic principles of multi-pathway regulation.Virulence · 2027Review
- Structural Bases for the Unconventional Activity of a Viroporin Channel.Biochemistry · 2026Article
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers.Biochemistry · 2022Article
- Requirement of a functional ion channel for Sindbis virus glycoprotein transport, CPV-II formation, and efficient virus budding.PLoS pathogens · 2022Article
- Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2.The international journal of biochemistry & cell biology · 2022Review
- SPCS1-Dependent E2-p7 processing determines HCV Assembly efficiency.PLoS pathogens · 2022Article
- Acetonitrile allows indirect replacement of nondeuterated lipid detergents by deuterated lipid detergents for the nuclear magnetic resonance study of detergent-soluble proteins.Protein science : a publication of the Protein Society · 2021Article
- Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease.Viruses · 2021Review
- Electrophysiological Properties from Computations at a Single Voltage: Testing Theory with Stochastic Simulations.Entropy (Basel, Switzerland) · 2021Article
- Inhibitor Development against p7 Channel in Hepatitis C Virus.Molecules (Basel, Switzerland) · 2021Article
- SFTSV Infection Induced Interleukin-1β Secretion Through NLRP3 Inflammasome Activation.Frontiers in immunology · 2021Article
- Article
- Critical Effect of the Detergent:Protein Ratio on the Formation of the Hepatitis C Virus p7 Channel.Biochemistry · 2019Review
- Hepatitis C virus sequence divergence preserves p7 viroporin structural and dynamic features.Scientific reports · 2019Article
- The Good, the Bad, and the Shocking: The Multiple Roles of Dengue Virus Nonstructural Protein 1 in Protection and Pathogenesis.Annual review of virology · 2018Review
- All-atom virus simulations.Current opinion in virology · 2018Review
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- The Unusual Transmembrane Partition of the Hexameric Channel of the Hepatitis C Virus.Structure (London, England : 1993) · 2018Article
- Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7.Drug design, development and therapy · 2018Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
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.
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