4g8l: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4g8l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G8L FirstGlance]. <br>
<table><tr><td colspan='2'>[[4g8l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G8L FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25A:5-O-MONOPHOSPHORYLADENYLYL(2- 5)ADENYLYL(2- 5)ADENOSINE'>25A</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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25A:5-O-MONOPHOSPHORYLADENYLYL(2- 5)ADENYLYL(2- 5)ADENOSINE'>25A</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=4g8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8l OCA], [https://pdbe.org/4g8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g8l RCSB], [https://www.ebi.ac.uk/pdbsum/4g8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8l 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=4g8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8l OCA], [https://pdbe.org/4g8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g8l RCSB], [https://www.ebi.ac.uk/pdbsum/4g8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8l ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/RN5A_HUMAN RN5A_HUMAN] Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. Might play a central role in the regulation of mRNA turnover.<ref>PMID:11585831</ref>  
[https://www.uniprot.org/uniprot/RN5A_HUMAN RN5A_HUMAN] Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. Might play a central role in the regulation of mRNA turnover.<ref>PMID:11585831</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
2',5'-linked oligoadenylates (2-5As) serve as conserved messengers of pathogen presence in the mammalian innate immune system. 2-5As induce self-association and activation of RNase L, which cleaves cytosolic RNA and promotes the production of interferons (IFNs) and cytokines driven by the transcription factors IRF-3 and NF-kappaB. We report that human RNase L is activated by forming high-order complexes, reminiscent of the mode of activation of the phylogenetically related transmembrane kinase/RNase Ire1 in the unfolded protein response. We describe crystal structures determined at 2.4 A and 2.8 A resolution, which show that two molecules of 2-5A at a time tether RNase L monomers via the ankyrin-repeat (ANK) domain. Each ANK domain harbors two distinct sites for 2-5A recognition that reside 50 A apart. These data reveal a function for the ANK domain as a 2-5A-sensing homo-oligomerization device and describe a nonlinear, ultrasensitive regulation in the 2-5A/RNase L system poised for amplification of the IFN response.
Innate Immune Messenger 2-5A Tethers Human RNase L into Active High-Order Complexes.,Han Y, Whitney G, Donovan J, Korennykh A Cell Rep. 2012 Oct 25;2(4):902-13. doi: 10.1016/j.celrep.2012.09.004. Epub 2012, Oct 19. PMID:23084743<ref>PMID:23084743</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4g8l" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 15:40, 14 March 2024

Active state of intact sensor domain of human RNase L with 2-5A bound

4g8l, resolution 2.80Å

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