4rez: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the Middle-East respiratory syndrome coronavirus papain-like protease== | ==Crystal structure of the Middle-East respiratory syndrome coronavirus papain-like protease== | ||
<StructureSection load='4rez' size='340' side='right' caption='[[4rez]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4rez' size='340' side='right'caption='[[4rez]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4rez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4REZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4REZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[4rez]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_betacoronavirus_2c_jordan-n3/2012 Human betacoronavirus 2c jordan-n3/2012]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4REZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4REZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</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"><scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rf0|4rf0]], [[4rf1|4rf1]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rf0|4rf0]], [[4rf1|4rf1]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF1ab ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1306931 Human betacoronavirus 2c Jordan-N3/2012])</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=4rez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rez OCA], [http://pdbe.org/4rez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rez RCSB], [http://www.ebi.ac.uk/pdbsum/4rez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rez 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=4rez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rez OCA], [http://pdbe.org/4rez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rez RCSB], [http://www.ebi.ac.uk/pdbsum/4rez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rez ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 17: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 4rez" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4rez" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human betacoronavirus 2c jordan-n3/2012]] | |||
[[Category: Large Structures]] | |||
[[Category: Bailey-Elkin, B A]] | [[Category: Bailey-Elkin, B A]] | ||
[[Category: Johnson, G G]] | [[Category: Johnson, G G]] | ||
Revision as of 13:19, 1 May 2019
Structural highlights
Publication Abstract from PubMedMiddle-East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging human pathogen that was first isolated in 2012. MERS-CoV replication depends in part on a virus-encoded papain-like protease (PLpro) that cleaves the viral replicase polyproteins at three sites releasing non-structural protein (nsp) 1, nsp2 and nsp3. In addition to this replicative function, MERS-CoV PLpro was recently shown to possess deubiquitinating (DUB) and deISGylating activities, as previously reported for other coronaviral PLpro domains including that of severe acute respiratory syndrome-coronavirus (SARS-CoV). These activities have been suggested to suppress host antiviral responses during infection. To understand the molecular basis for ubiquitin (Ub) recognition and deconjugation by MERS-CoV PLpro, we determined its crystal structure in complex with Ub. Guided by this structure, mutations were introduced into PLpro to specifically disrupt Ub binding without affecting viral polyprotein cleavage, as determined using an in trans nsp3|4 cleavage assay. Having developed a strategy to selectively disable PLpro DUB activity, we were able to specifically examine the effects of this activity on the innate immune response. Whereas the wild-type PLpro domain was found to suppress IFN-beta promoter activation, PLpro variants specifically lacking DUB activity were no longer able to do so. These findings directly implicate the DUB function of PLpro, and not its proteolytic activity per se, in the inhibition of IFN-beta promoter activity. The ability to decouple the DUB activity of PLpro from its role in viral polyprotein processing now provides an approach to further dissect the role(s) of PLpro as a viral DUB during MERS-CoV infection. Crystal Structure of the MERS Coronavirus Papain-Like Protease Bound to Ubiquitin Facilitates Targeted Disruption of Deubiquitinating Activity to Demonstrate its Role in Innate Immune Suppression.,Bailey-Elkin BA, Knaap RC, Johnson GG, Dalebout TJ, Ninaber DK, van Kasteren PB, Bredenbeek PJ, Snijder EJ, Kikkert M, Mark BL J Biol Chem. 2014 Oct 15. pii: jbc.M114.609644. PMID:25320088[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||