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4cem

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{{STRUCTURE_4cem| PDB=4cem | SCENE= }}
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==Crystal structure of the first MIF4G domain of human nonsense mediated decay factor UPF2==
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===Crystal structure of the first MIF4G domain of human nonsense mediated decay factor UPF2===
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<StructureSection load='4cem' size='340' side='right' caption='[[4cem]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24271394}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4cem]] 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=4CEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CEM FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cek|4cek]]</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=4cem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cem RCSB], [http://www.ebi.ac.uk/pdbsum/4cem PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nonsense-mediated decay (NMD) is a eukaryotic quality control pathway, involving conserved proteins UPF1, UPF2 and UPF3b, which detects and degrades mRNAs with premature stop codons. Human UPF2 comprises three tandem MIF4G domains and a C-terminal UPF1 binding region. MIF4G-3 binds UPF3b, but the specific functions of MIF4G-1 and MIF4G-2 are unknown. Crystal structures show that both MIF4G-1 and MIF4G-2 contain N-terminal capping helices essential for stabilization of the 10-helix MIF4G core and that MIF4G-2 interacts with MIF4G-3, forming a rigid assembly. The UPF2/UPF3b/SMG1 complex is thought to activate the kinase SMG1 to phosphorylate UPF1 in vivo. We identify MIF4G-3 as the binding site and in vitro substrate of SMG1 kinase and show that a ternary UPF2 MIF4G-3/UPF3b/SMG1 complex can form in vitro. Whereas in vivo complementation assays show that MIF4G-1 and MIF4G-2 are essential for NMD, tethering assays reveal that UPF2 truncated to only MIF4G-3 and the UPF1-binding region can still partially accomplish NMD. Thus UPF2 MIF4G-1 and MIF4G-2 appear to have a crucial scaffolding role, while MIF4G-3 is the key module required for triggering NMD.
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==Function==
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Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2.,Clerici M, Deniaud A, Boehm V, Gehring NH, Schaffitzel C, Cusack S Nucleic Acids Res. 2013 Nov 23. PMID:24271394<ref>PMID:24271394</ref>
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[[http://www.uniprot.org/uniprot/RENT2_HUMAN RENT2_HUMAN]] Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.<ref>PMID:11163187</ref> <ref>PMID:16209946</ref> <ref>PMID:18066079</ref>
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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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[[4cem]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CEM OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:024271394</ref><references group="xtra"/><references/>
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__TOC__
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[[Category: Boehm, V.]]
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</StructureSection>
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[[Category: Clerici, M.]]
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[[Category: Human]]
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[[Category: Cusack, S.]]
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[[Category: Boehm, V]]
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[[Category: Deniaud, A.]]
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[[Category: Clerici, M]]
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[[Category: Gehring, N H.]]
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[[Category: Cusack, S]]
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[[Category: Schaffitzel, C.]]
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[[Category: Deniaud, A]]
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[[Category: Gehring, N H]]
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[[Category: Schaffitzel, C]]
[[Category: Transcription]]
[[Category: Transcription]]

Revision as of 16:36, 21 December 2014

Crystal structure of the first MIF4G domain of human nonsense mediated decay factor UPF2

4cem, resolution 2.60Å

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