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| | ==NMR structure of the in-plane membrane anchor domain [1-28] of the monotopic NonStructural Protein 5A (NS5A) from the Bovine Viral Diarrhea Virus (BVDV)== | | ==NMR structure of the in-plane membrane anchor domain [1-28] of the monotopic NonStructural Protein 5A (NS5A) from the Bovine Viral Diarrhea Virus (BVDV)== |
| - | <StructureSection load='2ajm' size='340' side='right'caption='[[2ajm]], [[NMR_Ensembles_of_Models | 9 NMR models]]' scene=''> | + | <StructureSection load='2ajm' size='340' side='right'caption='[[2ajm]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ajm]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AJM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ajm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovine_viral_diarrhea_virus_1-CP7 Bovine viral diarrhea virus 1-CP7]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AJM FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ajj|2ajj]], [[2ajn|2ajn]], [[2ajo|2ajo]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ajm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ajm OCA], [http://pdbe.org/2ajm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ajm RCSB], [http://www.ebi.ac.uk/pdbsum/2ajm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ajm ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ajm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ajm OCA], [https://pdbe.org/2ajm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ajm RCSB], [https://www.ebi.ac.uk/pdbsum/2ajm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ajm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/POLG_BVDVC POLG_BVDVC]] Initial binding to target cell probably involves interaction of E(rns) with glycosaminoglycans. E1 and/or E2 are responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis (By similarity). P7 forms a leader sequence to properly orient NS2 in the membrane (By similarity). Uncleaved NS2-3 is required for production of infectious virus. NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus. NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS4A is a cofactor for the NS3 protease activity (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome. | + | [https://www.uniprot.org/uniprot/POLG_BVDVC POLG_BVDVC] Initial binding to target cell probably involves interaction of E(rns) with glycosaminoglycans. E1 and/or E2 are responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis (By similarity). P7 forms a leader sequence to properly orient NS2 in the membrane (By similarity). Uncleaved NS2-3 is required for production of infectious virus. NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus. NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS4A is a cofactor for the NS3 protease activity (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Bovine viral diarrhea virus 1-CP7]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brass, V]] | + | [[Category: Brass V]] |
| - | [[Category: Chipot, C]] | + | [[Category: Chipot C]] |
| - | [[Category: Deleage, G]] | + | [[Category: Deleage G]] |
| - | [[Category: Montserret, R]] | + | [[Category: Montserret R]] |
| - | [[Category: Moradpour, D]] | + | [[Category: Moradpour D]] |
| - | [[Category: Penin, F]] | + | [[Category: Penin F]] |
| - | [[Category: Sapay, N]] | + | [[Category: Sapay N]] |
| - | [[Category: Amphipathic alpha-helix]]
| + | |
| - | [[Category: In-plane membrane anchor domain]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
POLG_BVDVC Initial binding to target cell probably involves interaction of E(rns) with glycosaminoglycans. E1 and/or E2 are responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis (By similarity). P7 forms a leader sequence to properly orient NS2 in the membrane (By similarity). Uncleaved NS2-3 is required for production of infectious virus. NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus. NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS4A is a cofactor for the NS3 protease activity (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome.
Publication Abstract from PubMed
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a monotopic membrane protein anchored to the membrane by an N-terminal in-plane amphipathic alpha-helix. This membrane anchor is essential for the assembly of a functional viral replication complex. Although amino acid sequences differ considerably, putative membrane anchors with amphipathic features were predicted in NS5A from related Flaviviridae family members, in particular bovine viral diarrhea virus (BVDV), the prototype representative of the genus Pestivirus. We report here the NMR structure of the membrane anchor 1-28 of NS5A from BVDV in the presence of different membrane mimetic media. This anchor includes a long amphipathic alpha-helix of 21 residues interacting in-plane with the membrane interface and including a putative flexible region. Molecular dynamic simulation at a water-dodecane interface used to mimic the surface separating a lipid bilayer and an aqueous medium demonstrated the stability of the helix orientation and the location at the hydrophobic-hydrophilic interface. The flexible region of the helix appears to be required to allow the most favorable interaction of hydrophobic and hydrophilic side chain residues with their respective environment at the membrane interface. Despite the lack of amino acid sequence similarity, this amphipathic helix shares common structural features with that of the HCV counterpart, including a stable, hydrophobic N-terminal segment separated from the more hydrophilic C-terminal segment by a local, flexible region. These structural conservations point toward conserved roles of the N-terminal in-plane membrane anchors of NS5A in replication complex formation of HCV, BVDV, and other related viruses.
NMR structure and molecular dynamics of the in-plane membrane anchor of nonstructural protein 5A from bovine viral diarrhea virus.,Sapay N, Montserret R, Chipot C, Brass V, Moradpour D, Deleage G, Penin F Biochemistry. 2006 Feb 21;45(7):2221-33. PMID:16475810[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sapay N, Montserret R, Chipot C, Brass V, Moradpour D, Deleage G, Penin F. NMR structure and molecular dynamics of the in-plane membrane anchor of nonstructural protein 5A from bovine viral diarrhea virus. Biochemistry. 2006 Feb 21;45(7):2221-33. PMID:16475810 doi:10.1021/bi0517685
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