4yoe
From Proteopedia
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| - | ''' | + | ==Structure of UP1 bound to RNA 5'-AGU-3'== |
| + | <StructureSection load='4yoe' size='340' side='right' caption='[[4yoe]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4yoe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOE FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yoe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yoe RCSB], [http://www.ebi.ac.uk/pdbsum/4yoe PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.<ref>PMID:17229681</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein is a multifunctional RNA binding protein implicated in a wide range of biological functions. Mechanisms and putative hnRNP A1-RNA interactions have been inferred primarily from the crystal structure of its UP1 domain bound to ssDNA. RNA stem loops represent an important class of known hnRNP A1 targets, yet little is known about the structural basis of hnRNP A1-RNA recognition. Here, we report the first high-resolution structure (1.92A) of UP1 bound to a 5'-AGU-3' trinucleotide that resembles sequence elements of several native hnRNP A1-RNA stem loop targets. UP1 interacts specifically with the AG dinucleotide sequence via a "nucleobase pocket" formed by the beta-sheet surface of RRM1 and the inter-RRM linker; RRM2 does not contact the RNA. The inter-RRM linker forms the lid of the nucleobase pocket and we show using structure-guided mutagenesis that the conserved salt-bridge interactions (R75:D155 and R88:D157) on the alpha-helical side of the RNA binding surface stabilize the linker in a geometry poised to bind RNA. We further investigated the structural basis of UP1 binding HIViSL3ESS3 by determining a structural model of the complex scored by small-angle X-ray scattering. UP1 docks on the apical loop of SL3ESS3 using its RRM1 domain and inter-RRM linker only. The biophysical implications of the structural model were tested by measuring kinetic binding parameters, where mutations introduced within the apical loop reduce binding affinities by slowing down the rate of complex formation. Collectively, the data presented here provide the first insights into hnRNP A1-RNA interactions. | ||
| - | The | + | The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein.,Morgan CE, Meagher JL, Levengood JD, Delproposto J, Rollins C, Stuckey JA, Tolbert BS J Mol Biol. 2015 May 21. pii: S0022-2836(15)00293-4. doi:, 10.1016/j.jmb.2015.05.009. PMID:26003924<ref>PMID:26003924</ref> |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Meagher, J L]] | ||
| + | [[Category: Stuckey, J A]] | ||
| + | [[Category: Alternative splicing]] | ||
| + | [[Category: Hnrnpa1]] | ||
| + | [[Category: Protein-rna recognition]] | ||
Revision as of 13:59, 10 June 2015
Structure of UP1 bound to RNA 5'-AGU-3'
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