2hzc

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[[Image:2hzc.gif|left|200px]]<br /><applet load="2hzc" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2hzc, resolution 1.47&Aring;" />
 
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'''Crystal structure of the N-terminal RRM of the U2AF large subunit'''<br />
 
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==Overview==
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==Crystal structure of the N-terminal RRM of the U2AF large subunit==
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The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant in complex with poly(U) RNA suggested that rearrangement of flexible side-chains or bound water molecules may contribute to degenerate Py-tract recognition by U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a conformational change to interact with the RNA. These pre-existing alternative conformations may contribute to the ability of U2AF(65) to recognize a variety of Py-tract sequences. This rare, high-resolution view of an important member of the RRM class of RNA-binding domains highlights the role of alternative side-chain conformations in RNA recognition.
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<StructureSection load='2hzc' size='340' side='right'caption='[[2hzc]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2hzc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2fzr 2fzr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HZC FirstGlance]. <br>
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2HZC 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=ZN:'>ZN</scene> and <scene name='pdbligand=P6G:'>P6G</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2FZR. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZC OCA].
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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]] 1.47&#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=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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==Reference==
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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=2hzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hzc OCA], [https://pdbe.org/2hzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hzc RCSB], [https://www.ebi.ac.uk/pdbsum/2hzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hzc ProSAT]</span></td></tr>
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Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif., Thickman KR, Sickmier EA, Kielkopf CL, J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17188295 17188295]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/U2AF2_HUMAN U2AF2_HUMAN] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:15009664</ref> <ref>PMID:19470458</ref> <ref>PMID:19574390</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/hz/2hzc_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2hzc ConSurf].
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<div style="clear:both"></div>
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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: Kielkopf, C L.]]
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[[Category: Kielkopf CL]]
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[[Category: Sickmier, E A.]]
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[[Category: Sickmier EA]]
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[[Category: Thickman, K R.]]
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[[Category: Thickman KR]]
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[[Category: P6G]]
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[[Category: ZN]]
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[[Category: alternative conformation]]
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[[Category: rna recognition]]
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[[Category: rna splicing]]
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[[Category: rrm]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:47:23 2008''
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Current revision

Crystal structure of the N-terminal RRM of the U2AF large subunit

PDB ID 2hzc

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