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| | ==Active state of intact sensor domain of human RNase L with 2-5A bound== | | ==Active state of intact sensor domain of human RNase L with 2-5A bound== |
| - | <StructureSection load='4g8l' size='340' side='right' caption='[[4g8l]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4g8l' size='340' side='right'caption='[[4g8l]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g8l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/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"><scene name='pdbligand=25A:5-O-MONOPHOSPHORYLADENYLYL(2- 5)ADENYLYL(2- 5)ADENOSINE'>25A</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g8k|4g8k]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNASEL, RNS4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4g8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8l OCA], [http://pdbe.org/4g8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g8l RCSB], [http://www.ebi.ac.uk/pdbsum/4g8l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RN5A_HUMAN RN5A_HUMAN]] Defects in RNASEL are a cause of susceptibility to prostate cancer hereditary type 1 (HPC1) [MIM:[http://omim.org/entry/601518 601518]]. It is a condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. | + | [https://www.uniprot.org/uniprot/RN5A_HUMAN RN5A_HUMAN] Defects in RNASEL are a cause of susceptibility to prostate cancer hereditary type 1 (HPC1) [MIM:[https://omim.org/entry/601518 601518]. It is a condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. |
| | == Function == | | == Function == |
| - | [[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4g8l" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4g8l" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Donovan, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Han, Y]] | + | [[Category: Donovan J]] |
| - | [[Category: Korennykh, A]] | + | [[Category: Han Y]] |
| - | [[Category: Whitney, G]] | + | [[Category: Korennykh A]] |
| - | [[Category: Ankyrin-repeat domain]]
| + | [[Category: Whitney G]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Single-stranded rna]]
| + | |
| Structural highlights
Disease
RN5A_HUMAN Defects in RNASEL are a cause of susceptibility to prostate cancer hereditary type 1 (HPC1) [MIM:601518. It is a condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Function
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Le Roy F, Bisbal C, Silhol M, Martinand C, Lebleu B, Salehzada T. The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells. J Biol Chem. 2001 Dec 21;276(51):48473-82. Epub 2001 Oct 3. PMID:11585831 doi:10.1074/jbc.M107482200
- ↑ Han Y, Whitney G, Donovan J, Korennykh A. Innate Immune Messenger 2-5A Tethers Human RNase L into Active High-Order Complexes. Cell Rep. 2012 Oct 25;2(4):902-13. doi: 10.1016/j.celrep.2012.09.004. Epub 2012, Oct 19. PMID:23084743 doi:http://dx.doi.org/10.1016/j.celrep.2012.09.004
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