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2wjy

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Revision as of 08:50, 1 July 2020

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

Structural highlights

2wjy is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2wjv, 2iyk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

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 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.

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^[6]

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

References

↑ 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
↑ Kaygun H, Marzluff WF. Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1. Nat Struct Mol Biol. 2005 Sep;12(9):794-800. Epub 2005 Aug 7. PMID:16086026 doi:http://dx.doi.org/10.1038/nsmb972
↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
↑ Franks TM, Singh G, Lykke-Andersen J. Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Cell. 2010 Dec 10;143(6):938-50. doi: 10.1016/j.cell.2010.11.043. PMID:21145460 doi:http://dx.doi.org/10.1016/j.cell.2010.11.043
↑ Chakrabarti S, Jayachandran U, Bonneau F, Fiorini F, Basquin C, Domcke S, Le Hir H, Conti E. Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2. Mol Cell. 2011 Mar 18;41(6):693-703. PMID:21419344 doi:10.1016/j.molcel.2011.02.010
↑ Clerici M, Mourao A, Gutsche I, Gehring NH, Hentze MW, Kulozik A, Kadlec J, Sattler M, Cusack S. Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2. EMBO J. 2009 Aug 5;28(15):2293-306. Epub 2009 Jun 25. PMID:19556969 doi:10.1038/emboj.2009.175

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wjy"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the complex between human nonsense mediated decay factors UPF1 and UPF2 Orthorhombic form==
-<StructureSection load='2wjy' size='340' side='right' caption='[[2wjy]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='2wjy' size='340' side='right'caption='[[2wjy]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2wjy]] is a 1 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=2WJY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WJY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2wjy]] is a 1 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=2WJY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WJY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wjv|2wjv]], [[2iyk|2iyk]]</td></tr>
-<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=2wjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wjy OCA], [http://pdbe.org/2wjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wjy RCSB], [http://www.ebi.ac.uk/pdbsum/2wjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wjy ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wjy OCA], [http://pdbe.org/2wjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wjy RCSB], [http://www.ebi.ac.uk/pdbsum/2wjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wjy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Helicase|Helicase]]
+*[[Helicase 3D structures|Helicase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Clerici, M]]
 [[Category: Cusack, S]]

2wjy

From Proteopedia

Revision as of 08:50, 1 July 2020

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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