1r7d: Difference between revisions

Revision as of 15:48, 21 February 2008

NMR structure of the membrane anchor domain (1-31) of the nonstructural protein 5A (NS5A) of hepatitis C virus (Ensemble of 51 structures, sample in 50% tfe)

OverviewOverview

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a membrane-associated, essential component of the viral replication complex. Here, we report the three-dimensional structure of the membrane anchor domain of NS5A as determined by NMR spectroscopy. An alpha-helix extending from amino acid residue 5 to 25 was observed in the presence of different membrane mimetic media. This helix exhibited a hydrophobic, Trprich side embedded in detergent micelles, while the polar, charged side was exposed to the solvent. Thus, the NS5A membrane anchor domain forms an in-plane amphipathic alpha-helix embedded in the cytosolic leaflet of the membrane bilayer. Interestingly, mutations affecting the positioning of fully conserved residues located at the cytosolic surface of the helix impaired HCV RNA replication without interfering with the membrane association of NS5A. In conclusion, the NS5A membrane anchor domain constitutes a unique platform that is likely involved in specific interactions essential for the assembly of the HCV replication complex and that may represent a novel target for antiviral intervention.

About this StructureAbout this Structure

1R7D is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

ReferenceReference

Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A., Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D, J Biol Chem. 2004 Sep 24;279(39):40835-43. Epub 2004 Jul 7. PMID:15247283

Page seeded by OCA on Thu Feb 21 14:47:53 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1r7d.jpg|left|200px]]<br /><applet load="1r7d" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1r7d.jpg|left|200px]]<br /><applet load="1r7d" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1r7d" />
 '''NMR structure of the membrane anchor domain (1-31) of the nonstructural protein 5A (NS5A) of hepatitis C virus (Ensemble of 51 structures, sample in 50% tfe)'''<br />
 ==Overview==
-Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a, membrane-associated, essential component of the viral replication complex., Here, we report the three-dimensional structure of the membrane anchor, domain of NS5A as determined by NMR spectroscopy. An alpha-helix extending, from amino acid residue 5 to 25 was observed in the presence of different, membrane mimetic media. This helix exhibited a hydrophobic, Trprich side, embedded in detergent micelles, while the polar, charged side was exposed, to the solvent. Thus, the NS5A membrane anchor domain forms an in-plane, amphipathic alpha-helix embedded in the cytosolic leaflet of the membrane, bilayer. Interestingly, mutations affecting the positioning of fully, conserved residues located at the cytosolic surface of the helix impaired, HCV RNA replication without interfering with the membrane association of, NS5A. In conclusion, the NS5A membrane anchor domain constitutes a unique, platform that is likely involved in specific interactions essential for, the assembly of the HCV replication complex and that may represent a novel, target for antiviral intervention.
+Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a membrane-associated, essential component of the viral replication complex. Here, we report the three-dimensional structure of the membrane anchor domain of NS5A as determined by NMR spectroscopy. An alpha-helix extending from amino acid residue 5 to 25 was observed in the presence of different membrane mimetic media. This helix exhibited a hydrophobic, Trprich side embedded in detergent micelles, while the polar, charged side was exposed to the solvent. Thus, the NS5A membrane anchor domain forms an in-plane amphipathic alpha-helix embedded in the cytosolic leaflet of the membrane bilayer. Interestingly, mutations affecting the positioning of fully conserved residues located at the cytosolic surface of the helix impaired HCV RNA replication without interfering with the membrane association of NS5A. In conclusion, the NS5A membrane anchor domain constitutes a unique platform that is likely involved in specific interactions essential for the assembly of the HCV replication complex and that may represent a novel target for antiviral intervention.
 ==About this Structure==
-R7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R7D OCA].
+R7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R7D OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Appel, N.]]
 [[Category: Bartenschlager, R.]]
-[[Category: Blum, H.E.]]
+[[Category: Blum, H E.]]
 [[Category: Brass, V.]]
 [[Category: Ficheux, D.]]
@@ Line 26: / Line 26: @@
 [[Category: peptide.]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:19:39 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:53 2008''