5tl6
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of SARS-CoV papain-like protease in complex with the C-terminal domain of human ISG15== | |
| + | <StructureSection load='5tl6' size='340' side='right' caption='[[5tl6]], [[Resolution|resolution]] 2.62Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5tl6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TL6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TL6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tl7|5tl7]], [[5tla|5tla]]</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=5tl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tl6 OCA], [http://pdbe.org/5tl6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tl6 RCSB], [http://www.ebi.ac.uk/pdbsum/5tl6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tl6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> [[http://www.uniprot.org/uniprot/ISG15_HUMAN ISG15_HUMAN]] Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections.<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</ref> In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (By similarity).<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Severe Acute and Middle East Respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication as well as antagonize the host innate-immune response. The latter function involves reversing post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon stimulated gene product 15 (ISG15). Ubiquitin is known to be highly conserved among eukaryotes but surprisingly ISG15 is highly divergent among animals. The ramifications of this sequence divergence to recognition of ISG15 by coronaviral papain-like protease at the structural and biochemical levels are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS-CoV and mouse hepatitis virus (MHV) was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronoavirus PLP's interface with ISG15 via SARS-CoV PLP in complex with the principle binding domain of human and mouse ISG15s. The first X-ray structure of the full-length mouse ISG15 protein is also reported and highlights a unique, twisted-hinge region of ISG15 that is not conserved in human ISG15 suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities amongst coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species. | ||
| - | + | Structural insights into the interaction of coronavirus papain-like proteases and interferon-stimulated gene product 15 from different species.,Daczkowski CM, Dzimianski JV, Clasman JR, Goodwin O, Mesecar AD, Pegan SD J Mol Biol. 2017 Apr 21. pii: S0022-2836(17)30187-0. doi:, 10.1016/j.jmb.2017.04.011. PMID:28438633<ref>PMID:28438633</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5tl6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Daczkowski, C M]] | ||
| + | [[Category: Dzimianski, J V]] | ||
| + | [[Category: Pegan, S D]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Signaling protein-hydrolase complex]] | ||
Revision as of 13:05, 4 May 2017
Crystal structure of SARS-CoV papain-like protease in complex with the C-terminal domain of human ISG15
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