4ed5

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4ed5, resolution 2.00Å ()
Ligands: , ,
Gene: ELAVL1, HUR (Homo sapiens)


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of the two N-terminal RRM domains of HuR complexed with RNA

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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]

About this Structure

4ed5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. 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

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