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4cyk

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Revision as of 17:45, 10 May 2016

Structural basis for binding of Pan3 to Pan2 and its function in mRNA recruitment and deadenylation

Structural highlights

4cyk is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[PAN3_YEAST] Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs.. PAN3 acts as a positive regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with PAB1. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The conserved eukaryotic Pan2-Pan3 deadenylation complex shortens cytoplasmic mRNA 3' polyA tails to regulate mRNA stability. Although the exonuclease activity resides in Pan2, efficient deadenylation requires Pan3. The mechanistic role of Pan3 is unclear. Here, we show that Pan3 binds RNA directly both through its pseudokinase/C-terminal domain and via an N-terminal zinc finger that binds polyA RNA specifically. In contrast, isolated Pan2 is unable to bind RNA. Pan3 binds to the region of Pan2 that links its N-terminal WD40 domain to the C-terminal part that contains the exonuclease, with a 2:1 stoichiometry. The crystal structure of the Pan2 linker region bound to a Pan3 homodimer shows how the unusual structural asymmetry of the Pan3 dimer is used to form an extensive high-affinity interaction. This binding allows Pan3 to supply Pan2 with substrate polyA RNA, facilitating efficient mRNA deadenylation by the intact Pan2-Pan3 complex.

Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation.,Wolf J, Valkov E, Allen MD, Meineke B, Gordiyenko Y, McLaughlin SH, Olsen TM, Robinson CV, Bycroft M, Stewart M, Passmore LA EMBO J. 2014 May 28. pii: e201488373. PMID:24872509^[6]

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

References

↑ Brown CE, Tarun SZ Jr, Boeck R, Sachs AB. PAN3 encodes a subunit of the Pab1p-dependent poly(A) nuclease in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Oct;16(10):5744-53. PMID:8816488
↑ Lowell JE, Rudner DZ, Sachs AB. 3'-UTR-dependent deadenylation by the yeast poly(A) nuclease. Genes Dev. 1992 Nov;6(11):2088-99. PMID:1358757
↑ Brown CE, Sachs AB. Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol Cell Biol. 1998 Nov;18(11):6548-59. PMID:9774670
↑ Hammet A, Pike BL, Heierhorst J. Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J Biol Chem. 2002 Jun 21;277(25):22469-74. Epub 2002 Apr 12. PMID:11953437 doi:http://dx.doi.org/10.1074/jbc.M202473200
↑ Dheur S, Nykamp KR, Viphakone N, Swanson MS, Minvielle-Sebastia L. Yeast mRNA Poly(A) tail length control can be reconstituted in vitro in the absence of Pab1p-dependent Poly(A) nuclease activity. J Biol Chem. 2005 Jul 1;280(26):24532-8. Epub 2005 May 12. PMID:15894541 doi:http://dx.doi.org/M504720200
↑ Wolf J, Valkov E, Allen MD, Meineke B, Gordiyenko Y, McLaughlin SH, Olsen TM, Robinson CV, Bycroft M, Stewart M, Passmore LA. Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation. EMBO J. 2014 May 28. pii: e201488373. PMID:24872509 doi:http://dx.doi.org/10.15252/embj.201488373

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/4cyk"

@@ Line 1: / Line 1: @@
 ==Structural basis for binding of Pan3 to Pan2 and its function in mRNA recruitment and deadenylation==
 <StructureSection load='4cyk' size='340' side='right' caption='[[4cyk]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4cyk]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CYK FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4cyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cyk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cyk RCSB], [http://www.ebi.ac.uk/pdbsum/4cyk PDBsum]</span></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=4cyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cyk OCA], [http://pdbe.org/4cyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cyk RCSB], [http://www.ebi.ac.uk/pdbsum/4cyk PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4cyk" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4cyk

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Revision as of 17:45, 10 May 2016

Structural basis for binding of Pan3 to Pan2 and its function in mRNA recruitment and deadenylation

Structural highlights

Function

Publication Abstract from PubMed

References

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