1h2v

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[[Image:1h2v.png|left|200px]]
 
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==Structure of the human nuclear cap-binding-complex (CBC)==
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The line below this paragraph, containing "STRUCTURE_1h2v", creates the "Structure Box" on the page.
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<StructureSection load='1h2v' size='340' side='right'caption='[[1h2v]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1h2v]] 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=1H2V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H2V 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]] 2&#8491;</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=1h2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2v OCA], [https://pdbe.org/1h2v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h2v RCSB], [https://www.ebi.ac.uk/pdbsum/1h2v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2v ProSAT]</span></td></tr>
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{{STRUCTURE_1h2v| PDB=1h2v | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NCBP1_HUMAN NCBP1_HUMAN] Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure.<ref>PMID:8069914</ref> <ref>PMID:7651522</ref> <ref>PMID:11551508</ref> <ref>PMID:15059963</ref> <ref>PMID:15361857</ref> <ref>PMID:16186820</ref> <ref>PMID:17190602</ref> <ref>PMID:16317009</ref> <ref>PMID:17873884</ref> <ref>PMID:18369367</ref> <ref>PMID:19632182</ref> <ref>PMID:19648179</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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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/1h2v_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=1h2v 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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The heterodimeric nuclear cap-binding complex (CBC) binds to the 5' cap structure of RNAs in the nucleus and plays a central role in their diverse maturation steps. We describe the crystal structure at 2.1 A resolution of human CBC bound to an m(7)GpppG cap analogue. Comparison with the structure of uncomplexed CBC shows that cap binding induces co-operative folding around the dinucleotide of some 50 residues from the N- and C-terminal extensions to the central RNP domain of the small subunit CBP20. The cap-bound conformation of CBP20 is stabilized by an intricate network of interactions both to the ligand and within the subunit, as well as new interactions of the CBP20 N-terminal tail with the large subunit CBP80. Although the structure is very different from that of other known cap-binding proteins, such as the cytoplasmic cap-binding protein eIF4E, specificity for the methylated guanosine again is achieved by sandwiching the base between two aromatic residues, in this case two conserved tyrosines. Implications for the transfer of capped mRNAs to eIF4E, required for translation initiation, are discussed.
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===STRUCTURE OF THE HUMAN NUCLEAR CAP-BINDING-COMPLEX (CBC)===
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Large-scale induced fit recognition of an m(7)GpppG cap analogue by the human nuclear cap-binding complex.,Mazza C, Segref A, Mattaj IW, Cusack S EMBO J. 2002 Oct 15;21(20):5548-57. PMID:12374755<ref>PMID:12374755</ref>
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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 1h2v" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 12374755 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12374755}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[1h2v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H2V OCA].
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==Reference==
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<ref group="xtra">PMID:12374755</ref><ref group="xtra">PMID:12454499</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cusack, S.]]
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[[Category: Large Structures]]
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[[Category: Mattaj, I W.]]
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[[Category: Cusack S]]
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[[Category: Mazza, C.]]
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[[Category: Mattaj IW]]
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[[Category: Segref, A.]]
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[[Category: Mazza C]]
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[[Category: Cap-binding-complex]]
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[[Category: Segref A]]
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[[Category: Mif4g domain]]
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[[Category: Nuclear protein]]
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[[Category: Rna export]]
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[[Category: Rna maturation]]
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[[Category: Rna-binding]]
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[[Category: Rnp domain]]
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Current revision

Structure of the human nuclear cap-binding-complex (CBC)

PDB ID 1h2v

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