Acta Crystallographica Section D

Biological Crystallography

Volume 69, Part 3 (March 2013)

research papers

Acta Cryst. (2013). D69, 373-380    [ doi:10.1107/S0907444912047828 ]

The structure of the ARE-binding domains of Hu antigen R (HuR) undergoes conformational changes during RNA binding

H. Wang, F. Zeng, Q. Liu, H. Liu, Z. Liu, L. Niu, M. Teng and X. Li

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.

PDB references: 4egl and 4ed5

Keywords: HuR; RRM; RNA binding; conformational change.

pdfdisplay filedownload file

Portable Document Format (PDF) file (136.6 kbytes)
[ doi:10.1107/S0907444912047828/be5209sup1.pdf ]
Supplementary material


To open or display or play some files, you may need to set your browser up to use the appropriate software. See the full list of file types for an explanation of the different file types and their related mime types and, where available links to sites from where the appropriate software may be obtained.

The download button will force most browsers to prompt for a file name to store the data on your hard disk.

Where possible, images are represented by thumbnails.

 bibliographic record in  format