1uw4: Difference between revisions

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<StructureSection load='1uw4' size='340' side='right'caption='[[1uw4]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
<StructureSection load='1uw4' size='340' side='right'caption='[[1uw4]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1uw4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UW4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1uw4]] 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=1UW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UW4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uw4 OCA], [https://pdbe.org/1uw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uw4 RCSB], [https://www.ebi.ac.uk/pdbsum/1uw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uw4 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uw4 OCA], [https://pdbe.org/1uw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uw4 RCSB], [https://www.ebi.ac.uk/pdbsum/1uw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uw4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/REN3B_HUMAN REN3B_HUMAN]] FG syndrome;X-linked intellectual disability with marfanoid habitus;X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:17704778</ref>
[https://www.uniprot.org/uniprot/REN3B_HUMAN REN3B_HUMAN] FG syndrome;X-linked intellectual disability with marfanoid habitus;X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:17704778</ref>  
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/REN3B_HUMAN REN3B_HUMAN]] Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 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 UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core.<ref>PMID:11163187</ref> <ref>PMID:12718880</ref> <ref>PMID:16209946</ref> <ref>PMID:16601204</ref> <ref>PMID:18066079</ref> [[https://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> 
[https://www.uniprot.org/uniprot/REN3B_HUMAN REN3B_HUMAN] Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 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 UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core.<ref>PMID:11163187</ref> <ref>PMID:12718880</ref> <ref>PMID:16209946</ref> <ref>PMID:16601204</ref> <ref>PMID:18066079</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cusack, S]]
[[Category: Cusack S]]
[[Category: Izaurralde, E]]
[[Category: Izaurralde E]]
[[Category: Kadlec, J]]
[[Category: Kadlec J]]
[[Category: Mif4g domain]]
[[Category: Nmd]]
[[Category: Nonsense mediated mrna decay protein]]
[[Category: Rna binding protein]]
[[Category: Rna-binding protein]]
[[Category: Rnp domain]]

Latest revision as of 12:05, 9 May 2024

The structural basis of the interaction between nonsense mediated decay factors UPF2 and UPF3The structural basis of the interaction between nonsense mediated decay factors UPF2 and UPF3

Structural highlights

1uw4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.95Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

REN3B_HUMAN FG syndrome;X-linked intellectual disability with marfanoid habitus;X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.[1]

Function

REN3B_HUMAN Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 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 UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core.[2] [3] [4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast to human. We present a crystal structure at a resolution of 1.95 A of the complex between the interacting domains of human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain). The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the beta-sheet surface of the UPF3b RNP domain, which is generally used by these domains to bind nucleic acids. We show that the UPF3b RNP does not bind RNA, whereas the UPF2 construct and the complex do. Our results advance understanding of the molecular mechanisms underlying the NMD quality control process.

The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3.,Kadlec J, Izaurralde E, Cusack S Nat Struct Mol Biol. 2004 Apr;11(4):330-7. Epub 2004 Mar 7. PMID:15004547[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C, Edkins S, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Hills K, Jones D, Mironenko T, Perry J, Varian J, West S, Widaa S, Teague J, Dicks E, Butler A, Menzies A, Richardson D, Jenkinson A, Shepherd R, Raine K, Moon J, Luo Y, Parnau J, Bhat SS, Gardner A, Corbett M, Brooks D, Thomas P, Parkinson-Lawrence E, Porteous ME, Warner JP, Sanderson T, Pearson P, Simensen RJ, Skinner C, Hoganson G, Superneau D, Wooster R, Bobrow M, Turner G, Stevenson RE, Schwartz CE, Futreal PA, Srivastava AK, Stratton MR, Gecz J. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet. 2007 Sep;39(9):1127-33. Epub 2007 Aug 19. PMID:17704778 doi:http://dx.doi.org/10.1038/ng2100
  2. ↑ Lykke-Andersen J, Shu MD, Steitz JA. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000 Dec 22;103(7):1121-31. PMID:11163187
  3. ↑ Gehring NH, Neu-Yilik G, Schell T, Hentze MW, Kulozik AE. Y14 and hUpf3b form an NMD-activating complex. Mol Cell. 2003 Apr;11(4):939-49. PMID:12718880
  4. ↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
  5. ↑ Kunz JB, Neu-Yilik G, Hentze MW, Kulozik AE, Gehring NH. Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation. RNA. 2006 Jun;12(6):1015-22. Epub 2006 Apr 6. PMID:16601204 doi:http://dx.doi.org/10.1261/rna.12506
  6. ↑ Chamieh H, Ballut L, Bonneau F, Le Hir H. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nat Struct Mol Biol. 2008 Jan;15(1):85-93. Epub 2007 Dec 9. PMID:18066079 doi:http://dx.doi.org/10.1038/nsmb1330
  7. ↑ Kadlec J, Izaurralde E, Cusack S. The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3. Nat Struct Mol Biol. 2004 Apr;11(4):330-7. Epub 2004 Mar 7. PMID:15004547 doi:10.1038/nsmb741

1uw4, resolution 1.95Å

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