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| | ==Crystal structure of the Rous Associated Virus Integrase catalytic domain in MES buffer pH 6.0== | | ==Crystal structure of the Rous Associated Virus Integrase catalytic domain in MES buffer pH 6.0== |
| - | <StructureSection load='3o4n' size='340' side='right' caption='[[3o4n]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3o4n' size='340' side='right'caption='[[3o4n]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o4n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O4N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o4n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O4N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11886 Rous sarcoma virus])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11886 Rous sarcoma virus])</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=3o4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o4n OCA], [http://pdbe.org/3o4n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o4n RCSB], [http://www.ebi.ac.uk/pdbsum/3o4n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o4n 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=3o4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o4n OCA], [https://pdbe.org/3o4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o4n RCSB], [https://www.ebi.ac.uk/pdbsum/3o4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o4n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Retroviral Integrase|Retroviral Integrase]] | + | *[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Rous sarcoma virus]] | | [[Category: Rous sarcoma virus]] |
| | [[Category: Ballandras, A]] | | [[Category: Ballandras, A]] |
| Structural highlights
Publication Abstract from PubMed
Integrase (IN) is an important therapeutic target in the search for anti-Human Immunodeficiency Virus (HIV) inhibitors. This enzyme is composed of three domains and is hard to crystallize in its full form. First structural results on IN were obtained on the catalytic core domain (CCD) of the avian Rous and Sarcoma Virus strain Schmidt-Ruppin A (RSV-A) and on the CCD of HIV-1 IN. A ribonuclease-H like motif was revealed as well as a dimeric interface stabilized by two pairs of alpha-helices (alpha1/alpha5, alpha5/alpha1). These structural features have been validated in other structures of IN CCDs. We have determined the crystal structure of the Rous-associated virus type-1 (RAV-1) IN CCD to 1.8 A resolution. RAV-1 IN shows a standard activity for integration and its CCD differs in sequence from that of RSV-A by a single accessible residue in position 182 (substitution A182T). Surprisingly, the CCD of RAV-1 IN associates itself with an unexpected dimeric interface characterized by three pairs of alpha-helices (alpha3/alpha5, alpha1/alpha1, alpha5/alpha3). A182 is not involved in this novel interface, which results from a rigid body rearrangement of the protein at its alpha1, alpha3, alpha5 surface. A new basic groove that is suitable for single-stranded nucleic acid binding is observed at the surface of the dimer. We have subsequently determined the structure of the mutant A182T of RAV-1 IN CCD and obtained a RSV-A IN CCD-like structure with two pairs of buried alpha-helices at the interface. Our results suggest that the CCD of avian INs can dimerize in more than one state. Such flexibility can further explain the multifunctionality of retroviral INs, which beside integration of dsDNA are implicated in different steps of the retroviral cycle in presence of viral ssRNA.
A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly.,Ballandras A, Moreau K, Robert X, Confort MP, Merceron R, Haser R, Ronfort C, Gouet P PLoS One. 2011;6(8):e23032. Epub 2011 Aug 9. PMID:21857987[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ballandras A, Moreau K, Robert X, Confort MP, Merceron R, Haser R, Ronfort C, Gouet P. A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. PLoS One. 2011;6(8):e23032. Epub 2011 Aug 9. PMID:21857987 doi:10.1371/journal.pone.0023032
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