5ith

TIA-1 RRM2 recognition of target oligonucleotide

spinqualitylabelsall models 5ith, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ith is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.31Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TIA1_HUMAN Involved in alternative pre-RNA splicing and regulation of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs). Possesses nucleolytic activity against cytotoxic lymphocyte target cells. May be involved in apoptosis. Publication Abstract from PubMed TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with specificity for U-rich sequences directed by RRM2. It has recently been shown that RRM3 also contributes to binding, with preferential binding for C-rich sequences. Here we designed UC-rich and CU-rich 10-nt sequences for engagement of both RRM2 and RRM3 and demonstrated that the TIA-1 RRM23 construct preferentially binds the UC-rich RNA ligand (5-UUUUUACUCC-3). Interestingly, this binding depends on the presence of Lys274 that is C-terminal to RRM3 and binding to equivalent DNA sequences occurs with similar affinity. Small-angle X-ray scattering was used to demonstrate that, upon complex formation with target RNA or DNA, TIA-1 RRM23 adopts a compact structure, showing that both RRMs engage with the target 10-nt sequences to form the complex. We also report the crystal structure of TIA-1 RRM2 in complex with DNA to 2.3 A resolution providing the first atomic resolution structure of any TIA protein RRM in complex with oligonucleotide. Together our data support a specific mode of TIA-1 RRM23 interaction with target oligonucleotides consistent with the role of TIA-1 in binding RNA to regulate gene expression. TIA-1 RRM23 binding and recognition of target oligonucleotides.,Waris S, Garcia-Maurino SM, Sivakumaran A, Beckham SA, Loughlin FE, Gorospe M, Diaz-Moreno I, Wilce MCJ, Wilce JA Nucleic Acids Res. 2017 May 5;45(8):4944-4957. doi: 10.1093/nar/gkx102. PMID:28184449 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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