6y3z

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the Pby1 ATP-grasp enzyme bound to the S. cerevisiae mRNA decapping complex (Dcp1-Dcp2-Edc3)

Structural highlights

6y3z is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.49Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DCP1_YEAST Component of the decapping complex necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Decapping is the major pathway of mRNA degradation in yeast. It occurs through deadenylation, decapping and subsequent 5' to 3' exonucleolytic decay of the transcript body. DCP1 is activated by the DEAD-box helicase DHH1 and destabilizes the eIF-4F cap-binding complex from the mRNA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16]

Publication Abstract from PubMed

Most eukaryotic mRNAs harbor a characteristic 5' m7GpppN cap that promotes pre-mRNA splicing, mRNA nucleocytoplasmic transport and translation while also protecting mRNAs from exonucleolytic attacks. mRNA caps are eliminated by Dcp2 during mRNA decay, allowing 5'-3' exonucleases to degrade mRNA bodies. However, the Dcp2 decapping enzyme is poorly active on its own and requires binding to stable or transient protein partners to sever the cap of target mRNAs. Here, we analyse the role of one of these partners, the yeast Pby1 factor, which is known to co-localize into P-bodies together with decapping factors. We report that Pby1 uses its C-terminal domain to directly bind to the decapping enzyme. We solved the structure of this Pby1 domain alone and bound to the Dcp1-Dcp2-Edc3 decapping complex. Structure-based mutant analyses reveal that Pby1 binding to the decapping enzyme is required for its recruitment into P-bodies. Moreover, Pby1 binding to the decapping enzyme stimulates growth in conditions in which decapping activation is compromised. Our results point towards a direct connection of Pby1 with decapping and P-body formation, both stemming from its interaction with the Dcp1-Dcp2 holoenzyme.

Pby1 is a direct partner of the Dcp2 decapping enzyme.,Charenton C, Gaudon-Plesse C, Back R, Ulryck N, Cosson L, Seraphin B, Graille M Nucleic Acids Res. 2020 May 12. pii: 5836192. doi: 10.1093/nar/gkaa337. PMID:32396195^[17]

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

References

↑ Beelman CA, Stevens A, Caponigro G, LaGrandeur TE, Hatfield L, Fortner DM, Parker R. An essential component of the decapping enzyme required for normal rates of mRNA turnover. Nature. 1996 Aug 15;382(6592):642-6. PMID:8757137 doi:http://dx.doi.org/10.1038/382642a0
↑ Hatfield L, Beelman CA, Stevens A, Parker R. Mutations in trans-acting factors affecting mRNA decapping in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Oct;16(10):5830-8. PMID:8816497
↑ LaGrandeur TE, Parker R. Isolation and characterization of Dcp1p, the yeast mRNA decapping enzyme. EMBO J. 1998 Mar 2;17(5):1487-96. PMID:9482745 doi:http://dx.doi.org/10.1093/emboj/17.5.1487
↑ Anderson JS, Parker RP. The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex. EMBO J. 1998 Mar 2;17(5):1497-506. PMID:9482746 doi:10.1093/emboj/17.5.1497
↑ Dunckley T, Parker R. The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif. EMBO J. 1999 Oct 1;18(19):5411-22. PMID:10508173 doi:10.1093/emboj/18.19.5411
↑ Tharun S, Parker R. Analysis of mutations in the yeast mRNA decapping enzyme. Genetics. 1999 Apr;151(4):1273-85. PMID:10101156
↑ Zhang S, Williams CJ, Wormington M, Stevens A, Peltz SW. Monitoring mRNA decapping activity. Methods. 1999 Jan;17(1):46-51. PMID:10075882 doi:http://dx.doi.org/10.1006/meth.1998.0706
↑ Muhlrad D, Parker R. Recognition of yeast mRNAs as "nonsense containing" leads to both inhibition of mRNA translation and mRNA degradation: implications for the control of mRNA decapping. Mol Biol Cell. 1999 Nov;10(11):3971-8. PMID:10564284
↑ Schwartz DC, Parker R. Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of mRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Aug;19(8):5247-56. PMID:10409716
↑ Vilela C, Velasco C, Ptushkina M, McCarthy JE. The eukaryotic mRNA decapping protein Dcp1 interacts physically and functionally with the eIF4F translation initiation complex. EMBO J. 2000 Aug 15;19(16):4372-82. PMID:10944120 doi:http://dx.doi.org/10.1093/emboj/19.16.4372
↑ Dunckley T, Tucker M, Parker R. Two related proteins, Edc1p and Edc2p, stimulate mRNA decapping in Saccharomyces cerevisiae. Genetics. 2001 Jan;157(1):27-37. PMID:11139489
↑ Tharun S, Parker R. Targeting an mRNA for decapping: displacement of translation factors and association of the Lsm1p-7p complex on deadenylated yeast mRNAs. Mol Cell. 2001 Nov;8(5):1075-83. PMID:11741542
↑ Fischer N, Weis K. The DEAD box protein Dhh1 stimulates the decapping enzyme Dcp1. EMBO J. 2002 Jun 3;21(11):2788-97. PMID:12032091 doi:10.1093/emboj/21.11.2788
↑ Ramirez CV, Vilela C, Berthelot K, McCarthy JE. Modulation of eukaryotic mRNA stability via the cap-binding translation complex eIF4F. J Mol Biol. 2002 May 10;318(4):951-62. PMID:12054793 doi:http://dx.doi.org/10.1016/S0022-2836(02)00162-6
↑ Steiger M, Carr-Schmid A, Schwartz DC, Kiledjian M, Parker R. Analysis of recombinant yeast decapping enzyme. RNA. 2003 Feb;9(2):231-8. PMID:12554866
↑ Holmes LE, Campbell SG, De Long SK, Sachs AB, Ashe MP. Loss of translational control in yeast compromised for the major mRNA decay pathway. Mol Cell Biol. 2004 Apr;24(7):2998-3010. PMID:15024087
↑ Charenton C, Gaudon-Plesse C, Back R, Ulryck N, Cosson L, Seraphin B, Graille M. Pby1 is a direct partner of the Dcp2 decapping enzyme. Nucleic Acids Res. 2020 May 12. pii: 5836192. doi: 10.1093/nar/gkaa337. PMID:32396195 doi:http://dx.doi.org/10.1093/nar/gkaa337

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6y3z"

Categories: Large Structures | Saccharomyces cerevisiae S288C | Graille M

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6y3z is ON HOLD  until Paper Publication
+==Crystal structure of the Pby1 ATP-grasp enzyme bound to the S. cerevisiae mRNA decapping complex (Dcp1-Dcp2-Edc3)==
+<StructureSection load='6y3z' size='340' side='right'caption='[[6y3z]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6y3z]] 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=6Y3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y3Z 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]] 3.49&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6y3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y3z OCA], [https://pdbe.org/6y3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y3z RCSB], [https://www.ebi.ac.uk/pdbsum/6y3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y3z ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DCP1_YEAST DCP1_YEAST] Component of the decapping complex necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Decapping is the major pathway of mRNA degradation in yeast. It occurs through deadenylation, decapping and subsequent 5' to 3' exonucleolytic decay of the transcript body. DCP1 is activated by the DEAD-box helicase DHH1 and destabilizes the eIF-4F cap-binding complex from the mRNA.<ref>PMID:8757137</ref> <ref>PMID:8816497</ref> <ref>PMID:9482745</ref> <ref>PMID:9482746</ref> <ref>PMID:10508173</ref> <ref>PMID:10101156</ref> <ref>PMID:10075882</ref> <ref>PMID:10564284</ref> <ref>PMID:10409716</ref> <ref>PMID:10944120</ref> <ref>PMID:11139489</ref> <ref>PMID:11741542</ref> <ref>PMID:12032091</ref> <ref>PMID:12054793</ref> <ref>PMID:12554866</ref> <ref>PMID:15024087</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Most eukaryotic mRNAs harbor a characteristic 5' m7GpppN cap that promotes pre-mRNA splicing, mRNA nucleocytoplasmic transport and translation while also protecting mRNAs from exonucleolytic attacks. mRNA caps are eliminated by Dcp2 during mRNA decay, allowing 5'-3' exonucleases to degrade mRNA bodies. However, the Dcp2 decapping enzyme is poorly active on its own and requires binding to stable or transient protein partners to sever the cap of target mRNAs. Here, we analyse the role of one of these partners, the yeast Pby1 factor, which is known to co-localize into P-bodies together with decapping factors. We report that Pby1 uses its C-terminal domain to directly bind to the decapping enzyme. We solved the structure of this Pby1 domain alone and bound to the Dcp1-Dcp2-Edc3 decapping complex. Structure-based mutant analyses reveal that Pby1 binding to the decapping enzyme is required for its recruitment into P-bodies. Moreover, Pby1 binding to the decapping enzyme stimulates growth in conditions in which decapping activation is compromised. Our results point towards a direct connection of Pby1 with decapping and P-body formation, both stemming from its interaction with the Dcp1-Dcp2 holoenzyme.
-Authors:
+Pby1 is a direct partner of the Dcp2 decapping enzyme.,Charenton C, Gaudon-Plesse C, Back R, Ulryck N, Cosson L, Seraphin B, Graille M Nucleic Acids Res. 2020 May 12. pii: 5836192. doi: 10.1093/nar/gkaa337. PMID:32396195<ref>PMID:32396195</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6y3z" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Graille M]]

6y3z

From Proteopedia

Current revision

Crystal structure of the Pby1 ATP-grasp enzyme bound to the S. cerevisiae mRNA decapping complex (Dcp1-Dcp2-Edc3)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox