Related ArticlesNMR structure and ion channel activity of the p7 protein from hepatitis C virus.
J Biol Chem. 2010 Jul 28;
Authors: Montserret R, Saint N, Vanbelle C, Salvay AG, Simorre JP, Ebel C, Sapay N, Renisio JG, Bockmann A, Steinmann E, Pietschmann T, Dubuisson J, Chipot C, Penin F
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 alpha-helical, irrespective of the membrane mimetic medium, e.g. lysolipids, detergents, organic solvent-water mixtures. The secondary structure elements of the monomeric form of p7 were determined by 1H and 13C 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 to the phospholipid bilayer. These studies revealed the presence of a turn connecting an unexpected N-terminal alpha-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.
PMID: 20667830 [PubMed - as supplied by publisher]
Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.
Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.
Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.
J Mol Biol. 2010 Dec 14;
Authors: Chagot B, Chazin WJ
The function of the human voltage-gated sodium channel Na(V)1.5 is regulated in part by intracellular calcium signals. The ubiquitous calcium sensor protein calmodulin (CaM) is an important part of the complex calcium-sensing apparatus in Na(V)1.5. CaM interacts with an IQ...
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[NMR paper] Large structure rearrangement of colicin ia channel domain after membrane binding fro
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J Am Chem Soc. 2005 May 4;127(17):6402-8
Authors: Luo W, Yao X, Hong M
One of the main mechanisms of membrane protein folding is by spontaneous insertion into the lipid bilayer from the aqueous environment. The bacterial toxin, colicin Ia, is one such protein. To shed light on the conformational changes...
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[NMR paper] The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--fr
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Biopolymers. 2004;76(4):309-23
Authors: Tsantrizos YS
The virally encoded serine protease NS3/NS4A is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. Until very recently, the...
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[NMR paper] Hepatitis C virus NS3 protease requires its NS4A cofactor peptide for optimal binding
Hepatitis C virus NS3 protease requires its NS4A cofactor peptide for optimal binding of a boronic acid inhibitor as shown by NMR.
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Chem Biol. 2002 Jan;9(1):79-92
Authors: Archer SJ, Camac DM, Wu ZJ, Farrow NA, Domaille PJ, Wasserman ZR, Bukhtiyarova M, Rizzo C, Jagannathan S, Mersinger LJ, Kettner CA
NMR spectroscopy was used to characterize the hepatitis C virus (HCV) NS3 protease in a complex...
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[NMR paper] The NMR structure of the nucleocapsid protein from the mouse mammary tumor virus reve
The NMR structure of the nucleocapsid protein from the mouse mammary tumor virus reveals unusual folding of the C-terminal zinc knuckle.
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Biochemistry. 2000 Feb 22;39(7):1604-12
Authors: Klein DJ, Johnson PE, Zollars ES, De Guzman RN, Summers MF
The nucleocapsid protein (NC) from the mouse mammary tumor virus (MMTV) has been overexpressed in Escherichia coli and purified to homogeneity for...
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11-18-2010 09:15 PM
Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel.
Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel.
Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel.
Biochem Biophys Res Commun. 2010 Sep 9;
Authors: Pielak RM, Chou JJ
The M2 protein of influenza A virus forms a proton-selective channel that is required for viral replication; it is also the target of the anti-influenza drugs, amantadine and rimantadine. Widespread drug-resistant mutants, however, has greatly compromised the effectiveness of these drugs. Here, we report the...
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[NMR paper] NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (
NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (type 1) Rev.
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Biochemistry. 1995 Jul 4;34(26):8242-9
Authors: Scanlon MJ, Fairlie DP, Craik DJ, Englebretsen DR, West ML
NMR spectroscopy has been used to solve the three-dimensional solution structure of a minimal RNA-binding domain of the Rev protein from the human immunodeficiency virus (type 1), an essential regulatory protein for viral...
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[NMR paper] Structure of influenza virus panhandle RNA studied by NMR spectroscopy and molecular
Structure of influenza virus panhandle RNA studied by NMR spectroscopy and molecular modeling.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final_free.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Structure of influenza virus panhandle RNA studied by NMR spectroscopy and molecular modeling.
Nucleic Acids Res. 1999 Mar 1;27(5):1392-7
Authors: Cheong HK, Cheong C, Lee YS, Seong BL,...
NMR structure and ion channel activity of the p7 protein from hepatitis C virus.
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