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| | <StructureSection load='6bed' size='340' side='right'caption='[[6bed]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='6bed' size='340' side='right'caption='[[6bed]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bed]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccw Vaccw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BED OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BED FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bed]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus_WR Vaccinia virus WR]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BED FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFP:RIFAMPICIN'>RFP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sam|3sam]], [[3saq|3saq]], [[6beb|6beb]], [[6bec|6bec]], [[6bee|6bee]], [[6bef|6bef]], [[6beg|6beg]], [[6beh|6beh]], [[6bei|6bei]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFP:RIFAMPICIN'>RFP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VACWR118, D13L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10254 VACCW])</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=6bed FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bed OCA], [https://pdbe.org/6bed PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bed RCSB], [https://www.ebi.ac.uk/pdbsum/6bed PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bed ProSAT]</span></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=6bed FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bed OCA], [http://pdbe.org/6bed PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bed RCSB], [http://www.ebi.ac.uk/pdbsum/6bed PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bed ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/D13_VACCW D13_VACCW]] Scaffold protein which forms a transitory spherical honeycomb lattice providing curvature and rigidity to the convex membrane of crescent and immature virions (IV). This association occurs concomitantly with viral membrane formation. Targeted by the drug rifampicin, which prevents the formation of this lattice, and hence virus morphogenesis. In the presence of rifampicin, irregularly shaped membranes that lack the honeycomb layer accumulate around areas of electron-dense viroplasm. This layer is lost from virions during maturation from IV to mature virion (MV), through the proteolysis of A17 N-terminus. | + | [https://www.uniprot.org/uniprot/D13_VACCW D13_VACCW] Scaffold protein which forms a transitory spherical honeycomb lattice providing curvature and rigidity to the convex membrane of crescent and immature virions (IV). This association occurs concomitantly with viral membrane formation. Targeted by the drug rifampicin, which prevents the formation of this lattice, and hence virus morphogenesis. In the presence of rifampicin, irregularly shaped membranes that lack the honeycomb layer accumulate around areas of electron-dense viroplasm. This layer is lost from virions during maturation from IV to mature virion (MV), through the proteolysis of A17 N-terminus. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Vaccw]] | + | [[Category: Vaccinia virus WR]] |
| - | [[Category: Accurso, C]] | + | [[Category: Accurso C]] |
| - | [[Category: Coulibaly, F]] | + | [[Category: Coulibaly F]] |
| - | [[Category: Garriga, D]] | + | [[Category: Garriga D]] |
| - | [[Category: Assembly]]
| + | |
| - | [[Category: Immature virion]]
| + | |
| - | [[Category: Poxvirus]]
| + | |
| - | [[Category: Rifampicin resistance]]
| + | |
| - | [[Category: Scaffolding protein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
D13_VACCW Scaffold protein which forms a transitory spherical honeycomb lattice providing curvature and rigidity to the convex membrane of crescent and immature virions (IV). This association occurs concomitantly with viral membrane formation. Targeted by the drug rifampicin, which prevents the formation of this lattice, and hence virus morphogenesis. In the presence of rifampicin, irregularly shaped membranes that lack the honeycomb layer accumulate around areas of electron-dense viroplasm. This layer is lost from virions during maturation from IV to mature virion (MV), through the proteolysis of A17 N-terminus.
Publication Abstract from PubMed
Poxviruses are large DNA viruses that cause disease in animals and humans. They differ from classical enveloped viruses, because their membrane is acquired from cytoplasmic membrane precursors assembled onto a viral protein scaffold formed by the D13 protein rather than budding through cellular compartments. It was found three decades ago that the antibiotic rifampicin blocks this process and prevents scaffold formation. To elucidate the mechanism of action of rifampicin, we have determined the crystal structures of six D13-rifamycin complexes. These structures reveal that rifamycin compounds bind to a phenylalanine-rich region, or F-ring, at the membrane-proximal opening of the central channel of the D13 trimer. We show by NMR, surface plasmon resonance (SPR), and site-directed mutagenesis that A17, a membrane-associated viral protein, mediates the recruitment of the D13 scaffold by also binding to the F-ring. This interaction is the target of rifampicin, which prevents A17 binding, explaining the inhibition of viral morphogenesis. The F-ring of D13 is both conserved in sequence in mammalian poxviruses and essential for interaction with A17, defining a target for the development of assembly inhibitors. The model of the A17-D13 interaction describes a two-component system for remodeling nascent membranes that may be conserved in other large and giant DNA viruses.
Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin.,Garriga D, Headey S, Accurso C, Gunzburg M, Scanlon M, Coulibaly F Proc Natl Acad Sci U S A. 2018 Aug 1. pii: 1810398115. doi:, 10.1073/pnas.1810398115. PMID:30068608[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garriga D, Headey S, Accurso C, Gunzburg M, Scanlon M, Coulibaly F. Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin. Proc Natl Acad Sci U S A. 2018 Aug 1. pii: 1810398115. doi:, 10.1073/pnas.1810398115. PMID:30068608 doi:http://dx.doi.org/10.1073/pnas.1810398115
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