View source for 3pkn


==Crystal structure of MLLE domain of poly(A) binding protein in complex with PAM2 motif of La-related protein 4 (LARP4)==
<StructureSection load='3pkn' size='340' side='right'caption='[[3pkn]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pkn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PKN 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3pkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pkn OCA], [https://pdbe.org/3pkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pkn RCSB], [https://www.ebi.ac.uk/pdbsum/3pkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pkn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PABP1_HUMAN PABP1_HUMAN] Binds the poly(A) tail of mRNA. May be involved in cytoplasmic regulatory processes of mRNA metabolism such as pre-mRNA splicing. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed.<ref>PMID:11051545</ref> <ref>PMID:18447585</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them from 3' end-mediated decay. We report that La-related protein-4 (LARP4) is a newly described factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal IPs from HeLa cells reveal that LARP4 interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all approximately 150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 with tryptophan (PAM2w) in place of the phenylalanine. Binding and NMR studies show that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2-protein activities by PABP as part of mRNA homeostasis.

LARP4 binds poly(A), interacts with poly(A)-binding protein MLLE domain via a variant PAM2w motif and can promote mRNA stability.,Yang R, Gaidamakov SA, Xie J, Lee J, Martino L, Kozlov G, Crawford AK, Russo AN, Conte MR, Gehring K, Maraia RJ Mol Cell Biol. 2010 Nov 22. PMID:21098120<ref>PMID:21098120</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pkn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gehring K]]
[[Category: Kozlov G]]
[[Category: Xie J]]