4ED5

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

Summary for 4ED5

• Entry DOI: 10.2210/pdb4ed5/pdb
• Descriptor: ELAV-like protein 1, 5'-R(*A*UP*UP*UP*UP*UP*AP*UP*UP*UP*U)-3', GLYCEROL, ... (6 entities in total)
• Functional Keywords: rrm, rna binding, nucleus, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q15717
• Total number of polymer chains: 4
• Total formula weight: 47265.61

Authors

Wang, H.,Zeng, F.,Liu, Q.,Niu, L.,Teng, M.,Li, X. (deposition date: 2012-03-27, release date: 2012-05-23, Last modification date: 2024-03-20)

Primary citation

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.,Sect.D, 69:373-380, 2013

PubMed Abstract: 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 Å resolution. The crystal structure of RRM1/2 complexed with target mRNA was also solved at 2.0 Å 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.

PubMed: 23519412
DOI: 10.1107/S0907444912047828

Experimental method

X-RAY DIFFRACTION (2 Å)