1wdy

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[[Image:1wdy.jpg|left|200px]]<br /><applet load="1wdy" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1wdy, resolution 1.80&Aring;" />
 
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'''Crystal structure of ribonuclease'''<br />
 
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==Overview==
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==Crystal structure of ribonuclease==
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An interferon-induced endoribonuclease, ribonuclease L (RNase L), is, implicated in both the molecular mechanism of action of interferon and the, fundamental control of RNA stability in mammalian cells. RNase L is, catalytically active only after binding to an unusual activator molecule, containing a 5'-phosphorylated 2',5'-linked oligoadenylate (2-5A), in the, N-terminal half. Here, we report the crystal structure of the N-terminal, ankyrin repeat domain (ANK) of human RNase L complexed with the activator, 2-5A. This is the first structural view of an ankyrin repeat structure, directly interacting with a nucleic acid, rather than with a protein. The, ANK domain folds into eight ankyrin repeat elements and forms an extended, curved structure with a concave surface. The 2-5A molecule is accommodated, at a concave site and directly interacts with ankyrin repeats 2-4., Interestingly, two structurally equivalent 2-5A binding motifs are found, at repeats 2 and 4. The structural basis for 2-5A recognition by ANK is, essential for designing stable 2-5As with a high likelihood of activating, RNase L.
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<StructureSection load='1wdy' size='340' side='right'caption='[[1wdy]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1wdy]] is a 1 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=1WDY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WDY FirstGlance]. <br>
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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]] 1.8&#8491;</td></tr>
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<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>
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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=1wdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wdy OCA], [https://pdbe.org/1wdy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wdy RCSB], [https://www.ebi.ac.uk/pdbsum/1wdy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wdy ProSAT]</span></td></tr>
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</table>
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== Disease ==
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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.
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== Function ==
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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/1wdy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wdy ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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An interferon-induced endoribonuclease, ribonuclease L (RNase L), is implicated in both the molecular mechanism of action of interferon and the fundamental control of RNA stability in mammalian cells. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5'-phosphorylated 2',5'-linked oligoadenylate (2-5A), in the N-terminal half. Here, we report the crystal structure of the N-terminal ankyrin repeat domain (ANK) of human RNase L complexed with the activator 2-5A. This is the first structural view of an ankyrin repeat structure directly interacting with a nucleic acid, rather than with a protein. The ANK domain folds into eight ankyrin repeat elements and forms an extended curved structure with a concave surface. The 2-5A molecule is accommodated at a concave site and directly interacts with ankyrin repeats 2-4. Interestingly, two structurally equivalent 2-5A binding motifs are found at repeats 2 and 4. The structural basis for 2-5A recognition by ANK is essential for designing stable 2-5As with a high likelihood of activating RNase L.
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==Disease==
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Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.,Tanaka N, Nakanishi M, Kusakabe Y, Goto Y, Kitade Y, Nakamura KT EMBO J. 2004 Oct 13;23(20):3929-38. Epub 2004 Sep 23. PMID:15385955<ref>PMID:15385955</ref>
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Known diseases associated with this structure: Prostate cancer 1, 176807 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180435 180435]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1WDY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=25A:'>25A</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WDY OCA].
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</div>
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<div class="pdbe-citations 1wdy" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L., Tanaka N, Nakanishi M, Kusakabe Y, Goto Y, Kitade Y, Nakamura KT, EMBO J. 2004 Oct 13;23(20):3929-38. Epub 2004 Sep 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15385955 15385955]
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*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Goto, Y.]]
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[[Category: Goto Y]]
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[[Category: Kitade, Y.]]
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[[Category: Kitade Y]]
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[[Category: Kusakabe, Y.]]
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[[Category: Kusakabe Y]]
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[[Category: Nakamura, K.T.]]
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[[Category: Nakamura KT]]
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[[Category: Nakanishi, M.]]
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[[Category: Nakanishi M]]
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[[Category: Tanaka, N.]]
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[[Category: Tanaka N]]
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[[Category: 25A]]
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[[Category: hydrolase]]
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[[Category: nuclease]]
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[[Category: rna-binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:05:47 2008''
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Current revision

Crystal structure of ribonuclease

PDB ID 1wdy

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