|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the two N-terminal RRM domains of HuR complexed with RNA== | | ==Crystal structure of the two N-terminal RRM domains of HuR complexed with RNA== |
| - | <StructureSection load='4ed5' size='340' side='right' caption='[[4ed5]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4ed5' size='340' side='right'caption='[[4ed5]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ed5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ED5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ED5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ed5]] is a 4 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=4ED5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ED5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M2M:1-METHOXY-2-(2-METHOXYETHOXY)ETHANE'>M2M</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M2M:1-METHOXY-2-(2-METHOXYETHOXY)ETHANE'>M2M</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ELAVL1, HUR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ed5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ed5 OCA], [https://pdbe.org/4ed5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ed5 RCSB], [https://www.ebi.ac.uk/pdbsum/4ed5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ed5 ProSAT]</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=4ed5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ed5 OCA], [http://pdbe.org/4ed5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ed5 RCSB], [http://www.ebi.ac.uk/pdbsum/4ed5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ed5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ELAV1_HUMAN ELAV1_HUMAN]] Involved in 3'-UTR ARE-mediated MYC stabilization. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, HUR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro.<ref>PMID:19029303</ref> | + | [[https://www.uniprot.org/uniprot/ELAV1_HUMAN ELAV1_HUMAN]] Involved in 3'-UTR ARE-mediated MYC stabilization. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, HUR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro.<ref>PMID:19029303</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Li, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Liu, Q]] | + | [[Category: Li X]] |
| - | [[Category: Niu, L]] | + | [[Category: Liu Q]] |
| - | [[Category: Teng, M]] | + | [[Category: Niu L]] |
| - | [[Category: Wang, H]] | + | [[Category: Teng M]] |
| - | [[Category: Zeng, F]] | + | [[Category: Wang H]] |
| - | [[Category: Nucleus]]
| + | [[Category: Zeng F]] |
| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna binding protein-rna complex]]
| + | |
| - | [[Category: Rrm]]
| + | |
| Structural highlights
Function
[ELAV1_HUMAN] Involved in 3'-UTR ARE-mediated MYC stabilization. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, HUR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro.[1]
Publication Abstract from PubMed
Human RNA-binding protein (HuR), a ubiquitously expressed member of the Hu protein family, plays an important role in mRNA degradation and has been implicated as a key post-transcriptional regulator. HuR contains three RNA-recognition motif (RRM) domains. The two N-terminal tandem RRM domains can selectively bind AU-rich elements (AREs), while the third RRM domain (RRM3) contributes to interactions with the poly-A tail of target mRNA and other ligands. Here, the X-ray structure of two methylated tandem RRM domains (RRM1/2) of HuR in their RNA-free form was solved at 2.9 A resolution. The crystal structure of RRM1/2 complexed with target mRNA was also solved at 2.0 A resolution; comparisons of the two structures show that HuR RRM1/2 undergoes conformational changes upon RNA binding. Fluorescence polarization assays (FPA) were used to study the protein-RNA interactions. Both the structure and the FPA analysis indicated that RRM1 is the primary ARE-binding domain in HuR and that the conformational changes induce subsequent contacts of the RNA substrate with the inter-domain linker and RRM2 which greatly improve the RNA-binding affinity of HuR.
The structure of the ARE-binding domains of Hu antigen R (HuR) undergoes conformational changes during RNA binding.,Wang H, Zeng F, Liu Q, Liu H, Liu Z, Niu L, Teng M, Li X Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):373-80. doi:, 10.1107/S0907444912047828. Epub 2013 Feb 16. PMID:23519412[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
- ↑ Wang H, Zeng F, Liu Q, Liu H, Liu Z, Niu L, Teng M, Li X. The structure of the ARE-binding domains of Hu antigen R (HuR) undergoes conformational changes during RNA binding. Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):373-80. doi:, 10.1107/S0907444912047828. Epub 2013 Feb 16. PMID:23519412 doi:http://dx.doi.org/10.1107/S0907444912047828
|
