|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6trq' size='340' side='right'caption='[[6trq]], [[Resolution|resolution]] 2.94Å' scene=''> | | <StructureSection load='6trq' size='340' side='right'caption='[[6trq]], [[Resolution|resolution]] 2.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6trq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TRQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TRQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6trq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TRQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G:L-GUANOSINE-5-MONOPHOSPHATE'>0G</scene>, <scene name='pdbligand=2PO:PHOSPHONATE'>2PO</scene>, <scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.944Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCS1, YLR270W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G:L-GUANOSINE-5-MONOPHOSPHATE'>0G</scene>, <scene name='pdbligand=2PO:PHOSPHONATE'>2PO</scene>, <scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-(N(7)-methyl_5'-triphosphoguanosine)-(mRNA)_diphosphatase 5'-(N(7)-methyl 5'-triphosphoguanosine)-(mRNA) diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.59 3.6.1.59] </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=6trq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6trq OCA], [https://pdbe.org/6trq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6trq RCSB], [https://www.ebi.ac.uk/pdbsum/6trq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6trq 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=6trq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6trq OCA], [http://pdbe.org/6trq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6trq RCSB], [http://www.ebi.ac.uk/pdbsum/6trq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6trq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCPS_YEAST DCPS_YEAST]] Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) and tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP) or tri-methyl guanosine nucleoside monophosphate (m3(2,2,7)GMP), respectively. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) and tri-methylguanosine diphosphate (m3(2,2,7)GDP) to (m(7)GMP) and m3(2,2,7)GMP, respectively (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCS1 to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. May also regulates the 5'->3' exoribonucleolytic mRNA decay pathway in a cap-independent manner. Negatively regulates trehalase activity.<ref>PMID:12198172</ref> <ref>PMID:14523240</ref> <ref>PMID:15240832</ref> <ref>PMID:15273322</ref> <ref>PMID:16260594</ref> <ref>PMID:16963086</ref> <ref>PMID:22985415</ref> | + | [https://www.uniprot.org/uniprot/DCPS_YEAST DCPS_YEAST] Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) and tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP) or tri-methyl guanosine nucleoside monophosphate (m3(2,2,7)GMP), respectively. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) and tri-methylguanosine diphosphate (m3(2,2,7)GDP) to (m(7)GMP) and m3(2,2,7)GMP, respectively (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCS1 to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. May also regulates the 5'->3' exoribonucleolytic mRNA decay pathway in a cap-independent manner. Negatively regulates trehalase activity.<ref>PMID:12198172</ref> <ref>PMID:14523240</ref> <ref>PMID:15240832</ref> <ref>PMID:15273322</ref> <ref>PMID:16260594</ref> <ref>PMID:16963086</ref> <ref>PMID:22985415</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fuchs, A L]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Neu, A]] | + | [[Category: Fuchs A-L]] |
| - | [[Category: Sprangers, R]] | + | [[Category: Neu A]] |
| - | [[Category: Decapping]] | + | [[Category: Sprangers R]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mrna decapping]]
| + | |
| - | [[Category: Mrna degradation]]
| + | |
| Structural highlights
Function
DCPS_YEAST Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) and tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP) or tri-methyl guanosine nucleoside monophosphate (m3(2,2,7)GMP), respectively. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) and tri-methylguanosine diphosphate (m3(2,2,7)GDP) to (m(7)GMP) and m3(2,2,7)GMP, respectively (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCS1 to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. May also regulates the 5'->3' exoribonucleolytic mRNA decay pathway in a cap-independent manner. Negatively regulates trehalase activity.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The 5' messenger RNA (mRNA) cap structure enhances translation and protects the transcript against exonucleolytic degradation. During mRNA turnover, this cap is removed from the mRNA. This decapping step is catalyzed by the Scavenger Decapping Enzyme (DcpS), in case the mRNA has been exonucleolyticly shortened from the 3' end by the exosome complex. Here, we show that DcpS only processes mRNA fragments that are shorter than three nucleotides in length. Based on a combination of methyl transverse relaxation optimized (TROSY) NMR spectroscopy and X-ray crystallography, we established that the DcpS substrate length-sensing mechanism is based on steric clashes between the enzyme and the third nucleotide of a capped mRNA. For longer mRNA substrates, these clashes prevent conformational changes in DcpS that are required for the formation of a catalytically competent active site. Point mutations that enlarge the space for the third nucleotide in the mRNA body enhance the activity of DcpS on longer mRNA species. We find that this mechanism to ensure that the enzyme is not active on translating long mRNAs is conserved from yeast to humans. Finally, we show that the products that the exosome releases after 3' to 5' degradation of the mRNA body are indeed short enough to be decapped by DcpS. Our data thus directly confirms the notion that mRNA products of the exosome are direct substrates for DcpS. In summary, we demonstrate a direct relationship between conformational changes and enzyme activity that is exploited to achieve substrate selectivity.
Molecular basis of the selective processing of short mRNA substrates by the DcpS mRNA decapping enzyme.,Fuchs AL, Wurm JP, Neu A, Sprangers R Proc Natl Acad Sci U S A. 2020 Jul 28. pii: 2009362117. doi:, 10.1073/pnas.2009362117. PMID:32723815[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu H, Rodgers ND, Jiao X, Kiledjian M. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 2002 Sep 2;21(17):4699-708. PMID:12198172
- ↑ van Dijk E, Le Hir H, Seraphin B. DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12081-6. Epub 2003 Oct 1. PMID:14523240 doi:http://dx.doi.org/10.1073/pnas.1635192100
- ↑ Malys N, Carroll K, Miyan J, Tollervey D, McCarthy JE. The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast. Nucleic Acids Res. 2004 Jul 7;32(12):3590-600. Print 2004. PMID:15240832 doi:http://dx.doi.org/10.1093/nar/gkh687
- ↑ Liu SW, Jiao X, Liu H, Gu M, Lima CD, Kiledjian M. Functional analysis of mRNA scavenger decapping enzymes. RNA. 2004 Sep;10(9):1412-22. Epub 2004 Jul 23. PMID:15273322 doi:http://dx.doi.org/10.1261/rna.7660804
- ↑ Liu H, Kiledjian M. Scavenger decapping activity facilitates 5' to 3' mRNA decay. Mol Cell Biol. 2005 Nov;25(22):9764-72. PMID:16260594 doi:http://dx.doi.org/10.1128/MCB.25.22.9764-9772.2005
- ↑ Malys N, McCarthy JE. Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies. J Mol Biol. 2006 Oct 20;363(2):370-82. Epub 2006 Aug 11. PMID:16963086 doi:http://dx.doi.org/10.1016/j.jmb.2006.08.015
- ↑ Wypijewska A, Bojarska E, Lukaszewicz M, Stepinski J, Jemielity J, Davis RE, Darzynkiewicz E. 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry. 2012 Oct 9;51(40):8003-13. doi: 10.1021/bi300781g. Epub 2012 Sep, 25. PMID:22985415 doi:http://dx.doi.org/10.1021/bi300781g
- ↑ Fuchs AL, Wurm JP, Neu A, Sprangers R. Molecular basis of the selective processing of short mRNA substrates by the DcpS mRNA decapping enzyme. Proc Natl Acad Sci U S A. 2020 Jul 28. pii: 2009362117. doi:, 10.1073/pnas.2009362117. PMID:32723815 doi:http://dx.doi.org/10.1073/pnas.2009362117
|
