1uw4: Difference between revisions
No edit summary |
No edit summary |
||
| (17 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==The structural basis of the interaction between nonsense mediated decay factors UPF2 and UPF3== | ||
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which | <StructureSection load='1uw4' size='340' side='right'caption='[[1uw4]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | |||
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</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> | |||
</table> | |||
== 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> | |||
== 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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uw/1uw4_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1uw4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:15004547</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1uw4" style="background-color:#fffaf0;"></div> | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Cusack | [[Category: Cusack S]] | ||
[[Category: Izaurralde | [[Category: Izaurralde E]] | ||
[[Category: Kadlec | [[Category: Kadlec J]] | ||