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| | ==Structure of a viral OTU domain protease bound to interferon-stimulated gene 15 (ISG15)== | | ==Structure of a viral OTU domain protease bound to interferon-stimulated gene 15 (ISG15)== |
| - | <StructureSection load='3pse' size='340' side='right' caption='[[3pse]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3pse' size='340' side='right'caption='[[3pse]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3pse]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Crimean-congo_hemorrhagic_fever_virus Crimean-congo hemorrhagic fever virus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PSE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PSE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3pse]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Crimean-Congo_hemorrhagic_fever_orthonairovirus Crimean-Congo hemorrhagic fever orthonairovirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PSE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3CN:3-AMINOPROPANE'>3CN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pt2|3pt2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3CN:3-AMINOPROPANE'>3CN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ISG15, G1P2, UCRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3pse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pse OCA], [https://pdbe.org/3pse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pse RCSB], [https://www.ebi.ac.uk/pdbsum/3pse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pse 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=3pse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pse OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pse RCSB], [http://www.ebi.ac.uk/pdbsum/3pse PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/L_CCHFI L_CCHFI] Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3pse" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Crimean-congo hemorrhagic fever virus]] | + | [[Category: Crimean-Congo hemorrhagic fever orthonairovirus]] |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Bacik, J P]] | + | [[Category: Large Structures]] |
| - | [[Category: Frias-Staheli, N]] | + | [[Category: Bacik JP]] |
| - | [[Category: Garcia-Sastre, A]] | + | [[Category: Frias-Staheli N]] |
| - | [[Category: James, T W]] | + | [[Category: Garcia-Sastre A]] |
| - | [[Category: Mark, B L]] | + | [[Category: James TW]] |
| - | [[Category: 3-aminopropane]]
| + | [[Category: Mark BL]] |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| - | [[Category: Intein-mediated ligation]]
| + | |
| - | [[Category: Viral deubiquitinase]]
| + | |
| Structural highlights
Function
L_CCHFI Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity.
Publication Abstract from PubMed
The attachment of ubiquitin (Ub) and the Ub-like (Ubl) molecule interferon-stimulated gene 15 (ISG15) to cellular proteins mediates important innate antiviral responses. Ovarian tumor (OTU) domain proteases from nairoviruses and arteriviruses were recently found to remove these molecules from host proteins, which inhibits Ub and ISG15-dependent antiviral pathways. This contrasts with the Ub-specific activity of known eukaryotic OTU-domain proteases. Here we describe crystal structures of a viral OTU domain from the highly pathogenic Crimean-Congo haemorrhagic fever virus (CCHFV) bound to Ub and to ISG15 at 2.5-A and 2.3-A resolution, respectively. The complexes provide a unique structural example of ISG15 bound to another protein and reveal the molecular mechanism of an ISG15 cross-reactive deubiquitinase. To accommodate structural differences between Ub and ISG15, the viral protease binds the beta-grasp folds of Ub and C-terminal Ub-like domain of ISG15 in an orientation that is rotated nearly 75 degrees with respect to that observed for Ub bound to a representative eukaryotic OTU domain from yeast. Distinct structural determinants necessary for binding either substrate were identified and allowed the reengineering of the viral OTU protease into enzymes with increased substrate specificity, either for Ub or for ISG15. Our findings now provide the basis to determine in vivo the relative contributions of deubiquitination and deISGylation to viral immune evasion tactics, and a structural template of a promiscuous deubiquitinase from a haemorrhagic fever virus that can be targeted for inhibition using small-molecule-based strategies.
Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease.,James TW, Frias-Staheli N, Bacik JP, Levingston Macleod JM, Khajehpour M, Garcia-Sastre A, Mark BL Proc Natl Acad Sci U S A. 2011 Jan 18. PMID:21245344[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ James TW, Frias-Staheli N, Bacik JP, Levingston Macleod JM, Khajehpour M, Garcia-Sastre A, Mark BL. Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease. Proc Natl Acad Sci U S A. 2011 Jan 18. PMID:21245344 doi:10.1073/pnas.1013388108
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