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==Structural basis for binding of Pan3 to Pan2 and its function in mRNA recruitment and deadenylation== | ==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 | <StructureSection load='4cyk' size='340' side='right'caption='[[4cyk]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<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 [ | <table><tr><td colspan='2'>[[4cyk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. 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 [https://proteopedia.org/fgij/fg.htm?mol=4CYK FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cyk OCA], [https://pdbe.org/4cyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cyk RCSB], [https://www.ebi.ac.uk/pdbsum/4cyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cyk ProSAT]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PAN3_YEAST 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.<ref>PMID:8816488</ref> <ref>PMID:1358757</ref> <ref>PMID:9774670</ref> <ref>PMID:11953437</ref> <ref>PMID:15894541</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24872509</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cyk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Allen | [[Category: Large Structures]] | ||
[[Category: Bycroft | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Gordiyenko | [[Category: Allen MD]] | ||
[[Category: McLaughlin | [[Category: Bycroft M]] | ||
[[Category: Meineke | [[Category: Gordiyenko Y]] | ||
[[Category: Olsen | [[Category: McLaughlin SH]] | ||
[[Category: Passmore | [[Category: Meineke B]] | ||
[[Category: Robinson | [[Category: Olsen TM]] | ||
[[Category: Stewart | [[Category: Passmore LA]] | ||
[[Category: Valkov | [[Category: Robinson CV]] | ||
[[Category: Wolf | [[Category: Stewart M]] | ||
[[Category: Valkov E]] | |||
[[Category: Wolf J]] | |||