4g8k

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==Intact sensor domain of human RNase L in the inactive signaling state==
==Intact sensor domain of human RNase L in the inactive signaling state==
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<StructureSection load='4g8k' size='340' side='right' caption='[[4g8k]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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<StructureSection load='4g8k' size='340' side='right'caption='[[4g8k]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4g8k]] is a 2 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=4G8K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G8K FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4g8k]] is a 2 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=4G8K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G8K FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g8l|4g8l]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4g8k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8k OCA], [https://pdbe.org/4g8k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g8k RCSB], [https://www.ebi.ac.uk/pdbsum/4g8k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8k ProSAT]</span></td></tr>
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<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=4g8k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8k OCA], [http://pdbe.org/4g8k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g8k RCSB], [http://www.ebi.ac.uk/pdbsum/4g8k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8k ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[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.
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[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 ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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==See Also==
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*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4g8k" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Donovan, J]]
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[[Category: Large Structures]]
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[[Category: Han, Y]]
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[[Category: Donovan J]]
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[[Category: Korennykh, A]]
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[[Category: Han Y]]
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[[Category: Whitney, G]]
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[[Category: Korennykh A]]
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[[Category: Ankyrin-repeat domain]]
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[[Category: Whitney G]]
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[[Category: Hydrolase]]
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[[Category: Single-stranded rna]]
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Current revision

Intact sensor domain of human RNase L in the inactive signaling state

PDB ID 4g8k

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