2wjv

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{{Seed}}
 
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[[Image:2wjv.jpg|left|200px]]
 
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==Crystal structure of the complex between human nonsense mediated decay factors UPF1 and UPF2==
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The line below this paragraph, containing "STRUCTURE_2wjv", creates the "Structure Box" on the page.
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<StructureSection load='2wjv' size='340' side='right'caption='[[2wjv]], [[Resolution|resolution]] 2.85&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'>[[2wjv]] is a 4 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=2WJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WJV FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.85&#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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{{STRUCTURE_2wjv| PDB=2wjv | SCENE= }}
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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=2wjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wjv OCA], [https://pdbe.org/2wjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wjv RCSB], [https://www.ebi.ac.uk/pdbsum/2wjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wjv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RENT1_HUMAN RENT1_HUMAN] RNA-dependent helicase and ATPase required for nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability.<ref>PMID:11163187</ref> <ref>PMID:16086026</ref> <ref>PMID:18172165</ref> <ref>PMID:21145460</ref> <ref>PMID:21419344</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/wj/2wjv_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=2wjv 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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Nonsense-mediated decay (NMD) is a eukaryotic quality control mechanism that degrades mRNAs carrying premature stop codons. In mammalian cells, NMD is triggered when UPF2 bound to UPF3 on a downstream exon junction complex interacts with UPF1 bound to a stalled ribosome. We report structural studies on the interaction between the C-terminal region of UPF2 and intact UPF1. Crystal structures, confirmed by EM and SAXS, show that the UPF1 CH-domain is docked onto its helicase domain in a fixed configuration. The C-terminal region of UPF2 is natively unfolded but binds through separated alpha-helical and beta-hairpin elements to the UPF1 CH-domain. The alpha-helical region binds sixfold more weakly than the beta-hairpin, whereas the combined elements bind 80-fold more tightly. Cellular assays show that NMD is severely affected by mutations disrupting the beta-hairpin binding, but not by those only affecting alpha-helix binding. We propose that the bipartite mode of UPF2 binding to UPF1 brings the ribosome and the EJC in close proximity by forming a tight complex after an initial weak encounter with either element.
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===CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN HUMAN NONSENSE MEDIATED DECAY FACTORS UPF1 AND UPF2===
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Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2.,Clerici M, Mourao A, Gutsche I, Gehring NH, Hentze MW, Kulozik A, Kadlec J, Sattler M, Cusack S EMBO J. 2009 Aug 5;28(15):2293-306. Epub 2009 Jun 25. PMID:19556969<ref>PMID:19556969</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 2wjv" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19556969}}, adds the Publication Abstract to the page
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*[[Helicase 3D structures|Helicase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19556969 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19556969}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2WJV is a 4 chains structure of sequences 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=2WJV OCA].
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==Reference==
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<ref group="xtra">PMID:19556969</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Clerici, M.]]
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[[Category: Large Structures]]
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[[Category: Cusack, S.]]
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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: Gutsche, I.]]
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[[Category: Gehring NH]]
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[[Category: Hentze, M W.]]
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[[Category: Gutsche I]]
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[[Category: Kadlec, J.]]
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[[Category: Hentze MW]]
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[[Category: Kulozik, A.]]
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[[Category: Kadlec J]]
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[[Category: Mourao, A.]]
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[[Category: Kulozik A]]
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[[Category: Sattler, M.]]
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[[Category: Mourao A]]
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[[Category: Alternative splicing]]
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[[Category: Sattler M]]
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[[Category: Atp-binding]]
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[[Category: Coiled coil]]
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[[Category: Cytoplasm]]
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[[Category: Helicase]]
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[[Category: Hydrolase]]
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[[Category: Metal-binding]]
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[[Category: Nonsense mediated decay]]
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[[Category: Nonsense-mediated mrna decay]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Rna-binding]]
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[[Category: Upf1]]
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[[Category: Upf2]]
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[[Category: Zinc]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 8 09:29:52 2009''
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Current revision

Crystal structure of the complex between human nonsense mediated decay factors UPF1 and UPF2

PDB ID 2wjv

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