2i7t

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[[Image:2i7t.jpg|left|200px]]<br /><applet load="2i7t" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2i7t, resolution 2.10&Aring;" />
 
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'''Structure of human CPSF-73'''<br />
 
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==Overview==
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==Structure of human CPSF-73==
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Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive, maturational processing, including cleavage and polyadenylation at the, 3'-end. Despite the characterization of many proteins that are required, for the cleavage reaction, the identity of the endonuclease is not known., Recent analyses indicated that the 73-kDa subunit of cleavage and, polyadenylation specificity factor (CPSF-73) might be the endonuclease for, this and related reactions, although no direct data confirmed this. Here, we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate, group of the substrate, and the related yeast protein CPSF-100 (Ydh1) at, 2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, a, metallo-beta-lactamase domain and a novel beta-CASP (named for, metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active site, of CPSF-73, with two zinc ions, is located at the interface of the two, domains. Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this, activity. Our studies provide the first direct experimental evidence that, CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
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<StructureSection load='2i7t' size='340' side='right'caption='[[2i7t]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2i7t]] 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=2I7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I7T FirstGlance]. <br>
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2I7T 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I7T 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]] 2.1&#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=SO4:SULFATE+ION'>SO4</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=2i7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i7t OCA], [https://pdbe.org/2i7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i7t RCSB], [https://www.ebi.ac.uk/pdbsum/2i7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i7t ProSAT]</span></td></tr>
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Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease., Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L, Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17128255 17128255]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CPSF3_HUMAN CPSF3_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner.<ref>PMID:14749727</ref> <ref>PMID:15037765</ref> <ref>PMID:18688255</ref> <ref>PMID:17128255</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/i7/2i7t_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=2i7t 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: Mandel, C.R.]]
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[[Category: Mandel CR]]
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[[Category: Tong, L.]]
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[[Category: Tong L]]
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[[Category: Zhang, H.]]
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[[Category: Zhang H]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: artemis]]
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[[Category: double-strand break repair]]
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[[Category: metallo-b-lactamase]]
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[[Category: polyadenylation]]
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[[Category: pre-mrna processing]]
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[[Category: v(d)j recombination]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:35:12 2008''
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Current revision

Structure of human CPSF-73

PDB ID 2i7t

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OCA

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