6ivd: Difference between revisions

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 <StructureSection load='6ivd' size='340' side='right'caption='[[6ivd]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ivd]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IVD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IVD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ivd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Transmissible_gastroenteritis_virus Transmissible gastroenteritis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IVD FirstGlance]. <br>
-</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=6ivd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ivd OCA], [http://pdbe.org/6ivd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ivd RCSB], [http://www.ebi.ac.uk/pdbsum/6ivd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ivd ProSAT]</span></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]] 1.975&#8491;</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=6ivd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ivd OCA], [https://pdbe.org/6ivd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ivd RCSB], [https://www.ebi.ac.uk/pdbsum/6ivd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ivd ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/R1A_CVPPU R1A_CVPPU] The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 (By similarity).  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-|-[SAGC]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK.  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).  Nsp9 is a ssRNA-binding protein (By similarity).
-Coronaviruses are enveloped, single-stranded RNA viruses that are distributed worldwide. They include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and the human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), many of which seriously endanger human health and well-being. Only alphacoronaviruses and betacoronaviruses harbor nonstructural protein 1 (nsp1), which performs multiple functions in inhibiting antiviral host responses. The role of the C terminus of betacoronavirus nsp1 in virulence has been characterized, but the location of the alphacoronavirus nsp1 region that is important for virulence remains unclear. Here, using TGEV nsp1 as a model to explore the function of this protein in alphacoronaviruses, we demonstrate that alphacoronavirus nsp1 inhibits host gene expression. Solving the crystal structure of full-length TGEV at 1.85 A resolution and conducting several biochemical analyses, we observed that a specific motif (amino acids 91-95) of alphacoronavirus nsp1 is a conserved region that inhibits host protein synthesis. Using a reverse-genetics system based on CRISPR/Cas9 technology to construct a recombinant TGEV in which this specific nsp1 motif was altered, we found that this mutation does not affect virus replication in cell culture, but significantly reduces TGEV pathogenicity pigs. Taken together, our findings suggest that alphacoronavirus nsp1 is an essential virulence determinant, providing a potential paradigm for the development of a new attenuated vaccine based on modified nsp1.
-A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence.,Shen Z, Wang G, Yang Y, Shi J, Fang L, Li F, Xiao S, Fu ZF, Peng G J Biol Chem. 2019 Jul 26. pii: RA119.009713. doi: 10.1074/jbc.RA119.009713. PMID:31350335<ref>PMID:31350335</ref>
+==See Also==
+*[[Nonstructural protein 3D structures|Nonstructural protein 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6ivd" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Peng, G Q]]
-[[Category: Shen, Z]]
-[[Category: Nsp1 mutant]]
 [[Category: Transmissible gastroenteritis virus]]
-[[Category: Viral protein]]
+[[Category: Peng GQ]]
+[[Category: Shen Z]]