View source for 3pt2


==Structure of a viral OTU domain protease bound to Ubiquitin==
<StructureSection load='3pt2' size='340' side='right'caption='[[3pt2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pt2]] 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=3PT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PT2 FirstGlance]. <br>
</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3pt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pt2 OCA], [https://pdbe.org/3pt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pt2 RCSB], [https://www.ebi.ac.uk/pdbsum/3pt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pt2 ProSAT]</span></td></tr>
</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.
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== 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<ref>PMID:21245344</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3pt2" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Crimean-Congo hemorrhagic fever orthonairovirus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bacik JP]]
[[Category: Frias-Staheli N]]
[[Category: Garcia-Sastre A]]
[[Category: James TW]]
[[Category: Mark BL]]