View source for 8smo


==Crystal structure of the complex between truncated MLLE domain of PABPC1 and engineered superPAM2 peptide==
<StructureSection load='8smo' size='340' side='right'caption='[[8smo]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8smo]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SMO 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=8smo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8smo OCA], [https://pdbe.org/8smo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8smo RCSB], [https://www.ebi.ac.uk/pdbsum/8smo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8smo 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> 
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== Publication Abstract from PubMed ==
The MLLE domain is a peptide-binding domain found in the poly(A) binding protein (PABP) and the ubiquitin protein E3 ligase N-recognin 5 (UBR5) that recognizes a conserved motif, named PABP-interacting motif 2 (PAM2). The majority of PAM2 sequences bind to MLLE domains with low-micromolar affinity. Here, we designed a chimeric PAM2 peptide termed super PAM2 (sPAM2) by combining classical and trinucleotide repeat-containing 6 (TNRC6)-like binding modes to create a superior binder for the MLLE domain. The crystal structure of the PABPC1 MLLE-sPAM2 complex shows a crucial role of conserved sPAM2 leucine, phenylalanine and tryptophan residues in the interaction. We used deep mutational scanning (DMS) coupled with isothermal titration calorimetry (ITC) to characterize the specificity profiles for PABPC1 and UBR5 MLLE. The best sPAM2 sequence binds to PABPC1 MLLE with low-nanomolar affinity and nearly 20-fold more tightly than the best natural PAM2 sequence. This suggests that the affinities of natural PAM2 sequences are tuned to control their binding to PABPC1 and UBR5. Our study will aid in the discovery of new PAM2-containing proteins (PACs) and facilitate in vivo studies of PAM2-mediated cellular pathways.

Deep Mutational Scanning of an Engineered High-affinity Ligand of the poly(A) Binding Protein MLLE Domain.,Behvarmanesh A, Kozlov G, Wagner JP, Chen YS, Gehring K J Mol Biol. 2025 Jun 15;437(12):169120. doi: 10.1016/j.jmb.2025.169120. Epub 2025 , Apr 1. PMID:40180125<ref>PMID:40180125</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8smo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Gehring K]]
[[Category: Kozlov G]]