5kq4

From Proteopedia

(Difference between revisions)

Revision as of 12:20, 25 December 2019

Crystal structure of S. pombe Dcp1/Dcp2 in complex with H. sapiens PNRC2 and synthetic cap analog

Structural highlights

5kq4 is a 6 chain structure with sequence from Fission yeast and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5kq1
Gene:	dcp1, SPBC3B9.21 (Fission yeast), PNRC2, HSPC208 (HUMAN), dcp2, SPAC19A8.12 (Fission yeast)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DCP1_SCHPO] 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.^[1] [DCP2_SCHPO] Catalytic 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.^[2] [PNRC2_HUMAN] Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs. Required for UPF1/RENT1 localization to the P-body. Also acts as a nuclear receptor coactivator. May play a role in controlling the energy balance between energy storage and energy expenditure.^[3] ^[4]

Publication Abstract from PubMed

Removal of the 5' cap on mRNA by the decapping enzyme Dcp2 is a critical step in 5'-to-3' mRNA decay. Understanding the structural basis of Dcp2 activity has been a challenge because Dcp2 is dynamic and has weak affinity for the cap substrate. Here we present a 2.6-A-resolution crystal structure of a heterotrimer of fission yeast Dcp2, its essential activator Dcp1, and the human NMD cofactor PNRC2, in complex with a tight-binding cap analog. Cap binding is accompanied by a conformational change in Dcp2, thereby forming a composite nucleotide-binding site comprising conserved residues in the catalytic and regulatory domains. Kinetic analysis of PNRC2 revealed that a conserved short linear motif enhances both substrate affinity and the catalytic step of decapping. These findings explain why Dcp2 requires a conformational change for efficient catalysis and reveals that coactivators promote RNA binding and the catalytic step of decapping, possibly through different conformational states.

Structural basis of mRNA-cap recognition by Dcp1-Dcp2.,Mugridge JS, Ziemniak M, Jemielity J, Gross JD Nat Struct Mol Biol. 2016 Oct 3. doi: 10.1038/nsmb.3301. PMID:27694842^[5]

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

References

↑ Sakuno T, Araki Y, Ohya Y, Kofuji S, Takahashi S, Hoshino S, Katada T. Decapping reaction of mRNA requires Dcp1 in fission yeast: its characterization in different species from yeast to human. J Biochem. 2004 Dec;136(6):805-12. PMID:15671491 doi:http://dx.doi.org/136/6/805
↑ Sakuno T, Araki Y, Ohya Y, Kofuji S, Takahashi S, Hoshino S, Katada T. Decapping reaction of mRNA requires Dcp1 in fission yeast: its characterization in different species from yeast to human. J Biochem. 2004 Dec;136(6):805-12. PMID:15671491 doi:http://dx.doi.org/136/6/805
↑ Zhou D, Chen S. PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an SH3-binding motif. Nucleic Acids Res. 2001 Oct 1;29(19):3939-48. PMID:11574675
↑ Cho H, Kim KM, Kim YK. Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Mol Cell. 2009 Jan 16;33(1):75-86. doi: 10.1016/j.molcel.2008.11.022. PMID:19150429 doi:http://dx.doi.org/10.1016/j.molcel.2008.11.022
↑ Mugridge JS, Ziemniak M, Jemielity J, Gross JD. Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nat Struct Mol Biol. 2016 Oct 3. doi: 10.1038/nsmb.3301. PMID:27694842 doi:http://dx.doi.org/10.1038/nsmb.3301

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/5kq4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of S. pombe Dcp1/Dcp2 in complex with H. sapiens PNRC2 and synthetic cap analog==
-<StructureSection load='5kq4' size='340' side='right' caption='[[5kq4]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
+<StructureSection load='5kq4' size='340' side='right'caption='[[5kq4]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kq4]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KQ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KQ4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kq4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Fission_yeast Fission yeast] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KQ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KQ4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6VQ:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-AZANYL-7-METHYL-6-OXIDANYLIDENE-3~{H}-PURIN-7-IUM-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-SULFANYL-PHOSPHORYL]+[[[(2~{R},3~{S},4~{R},5~{R})-5-(2-AZANYL-7-METHYL-6-OXIDANYLIDENE-3~{H}-PURIN-7-IUM-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-SULFANYL-PHOSPHORYL]OXY-OXIDANYL-PHOSPHORYL]+HYDROGEN+PHOSPHATE'>6VQ</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kq1|5kq1]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dcp1, SPBC3B9.21 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Fission yeast]), PNRC2, HSPC208 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), dcp2, SPAC19A8.12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Fission yeast])</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=5kq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kq4 OCA], [http://pdbe.org/5kq4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kq4 RCSB], [http://www.ebi.ac.uk/pdbsum/5kq4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kq4 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Fission yeast]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gross, J D]]
 [[Category: Jemielity, J]]

5kq4

From Proteopedia

Revision as of 12:20, 25 December 2019

Crystal structure of S. pombe Dcp1/Dcp2 in complex with H. sapiens PNRC2 and synthetic cap analog

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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