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| | ==Crystal Structure of the K3L Protein From Vaccinia Virus (Wisconsin Strain)== | | ==Crystal Structure of the K3L Protein From Vaccinia Virus (Wisconsin Strain)== |
| - | <StructureSection load='1luz' size='340' side='right' caption='[[1luz]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='1luz' size='340' side='right'caption='[[1luz]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1luz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccw Vaccw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LUZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1luz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus_WR Vaccinia virus WR]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LUZ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">K3L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10254 VACCW])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=1luz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1luz OCA], [http://pdbe.org/1luz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1luz RCSB], [http://www.ebi.ac.uk/pdbsum/1luz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1luz ProSAT]</span></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=1luz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1luz OCA], [https://pdbe.org/1luz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1luz RCSB], [https://www.ebi.ac.uk/pdbsum/1luz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1luz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/K3_VACCW K3_VACCW]] Viral mimic of eIF-2-alpha that acts as a pseudosubstrate for EIF2AK2/PKR kinase. Inhibits therefore eIF-2-alpha phosphorylation by host EIF2AK2/PKR kinase and prevents protein synthesis shutoff.<ref>PMID:8099586</ref> | + | [https://www.uniprot.org/uniprot/PG041_VACCW PG041_VACCW] Viral mimic of EIF2S1/eIF-2alpha that acts as a pseudosubstrate for EIF2AK2/PKR kinase (PubMed:8099586, PubMed:9199350). Inhibits therefore EIF2S1/eIF-2alpha phosphorylation by host EIF2AK2/PKR kinase and prevents protein synthesis shutoff (PubMed:8099586, PubMed:9199350). Determinant of host species specificity (PubMed:32056708).<ref>PMID:32056708</ref> <ref>PMID:8099586</ref> <ref>PMID:9199350</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/1luz_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/1luz_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vaccw]] | + | [[Category: Large Structures]] |
| - | [[Category: Dar, A C]] | + | [[Category: Vaccinia virus WR]] |
| - | [[Category: Sicheri, F]] | + | [[Category: Dar AC]] |
| - | [[Category: Stranded anti-parallel beta barrel]] | + | [[Category: Sicheri F]] |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
PG041_VACCW Viral mimic of EIF2S1/eIF-2alpha that acts as a pseudosubstrate for EIF2AK2/PKR kinase (PubMed:8099586, PubMed:9199350). Inhibits therefore EIF2S1/eIF-2alpha phosphorylation by host EIF2AK2/PKR kinase and prevents protein synthesis shutoff (PubMed:8099586, PubMed:9199350). Determinant of host species specificity (PubMed:32056708).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The vaccinia virus protein K3L subverts the mammalian antiviral defense mechanism by inhibiting the RNA-dependent protein kinase PKR. K3L is a structural mimic of PKR's natural substrate, the translation initiation factor eIF2alpha. To further our understanding of K3L inhibitory function and PKR substrate recognition, we have solved the 1.8 A X-ray crystal structure of K3L. The structure consists of a five-strand beta barrel with an intervening helix insert region similar in topology to the functionally divergent S1 domain. Mutational analysis identifies two proximal regions of the K3L structure as possessing specialized PKR binding and inhibitory function. Further analysis reveals that PKR dimerization composes a key switch that regulates both its catalytic activation and its molecular recognition of K3L and eIF2alpha.
X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition.,Dar AC, Sicheri F Mol Cell. 2002 Aug;10(2):295-305. PMID:12191475[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cao J, Varga J, Deschambault Y. Poxvirus encoded eIF2α homolog, K3 family proteins, is a key determinant of poxvirus host species specificity. Virology. 2020 Feb;541:101-112. PMID:32056708 doi:10.1016/j.virol.2019.12.008
- ↑ Carroll K, Elroy-Stein O, Moss B, Jagus R. Recombinant vaccinia virus K3L gene product prevents activation of double-stranded RNA-dependent, initiation factor 2 alpha-specific protein kinase. J Biol Chem. 1993 Jun 15;268(17):12837-42. PMID:8099586
- ↑ Kawagishi-Kobayashi M, Silverman JB, Ung TL, Dever TE. Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2alpha. Mol Cell Biol. 1997 Jul;17(7):4146-58. PMID:9199350 doi:10.1128/MCB.17.7.4146
- ↑ Dar AC, Sicheri F. X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition. Mol Cell. 2002 Aug;10(2):295-305. PMID:12191475
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