2RRB

Refinement of RNA binding domain in human Tra2 beta protein

Summary for 2RRB

• Entry DOI: 10.2210/pdb2rrb/pdb
• Related: 2RRA
• Descriptor: cDNA FLJ40872 fis, clone TUTER2000283, highly similar to Homo sapiens transformer-2-beta (SFRS10) gene (1 entity in total)
• Functional Keywords: rrm domain, rbd, rna binding protein, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 10891.19

Authors

Tsuda, K.,Kuwasako, K.,Takahashi, M.,Someya, T.,Inoue, M.,Kigawa, T.,Terada, T.,Shirouzu, M.,Sugano, S.,Muto, Y.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2010-06-17, release date: 2011-04-27, Last modification date: 2024-05-01)

Primary citation

Tsuda, K.,Someya, T.,Kuwasako, K.,Takahashi, M.,He, F.,Unzai, S.,Inoue, M.,Harada, T.,Watanabe, S.,Terada, T.,Kobayashi, N.,Shirouzu, M.,Kigawa, T.,Tanaka, A.,Sugano, S.,Guntert, P.,Yokoyama, S.,Muto, Y.
Structural basis for the dual RNA-recognition modes of human Tra2-beta RRM.
Nucleic Acids Res., 39:1538-1553, 2011

PubMed Abstract: Human Transformer2-β (hTra2-β) is an important member of the serine/arginine-rich protein family, and contains one RNA recognition motif (RRM). It controls the alternative splicing of several pre-mRNAs, including those of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Accordingly, the RRM of hTra2-β specifically binds to two types of RNA sequences [the CAA and (GAA)(2) sequences]. We determined the solution structure of the hTra2-β RRM (spanning residues Asn110-Thr201), which not only has a canonical RRM fold, but also an unusual alignment of the aromatic amino acids on the β-sheet surface. We then solved the complex structure of the hTra2-β RRM with the (GAA)(2) sequence, and found that the AGAA tetra-nucleotide was specifically recognized through hydrogen-bond formation with several amino acids on the N- and C-terminal extensions, as well as stacking interactions mediated by the unusually aligned aromatic rings on the β-sheet surface. Further NMR experiments revealed that the hTra2-β RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-β RRM recognizes two types of RNA sequences in different RNA binding modes.

PubMed: 20926394
DOI: 10.1093/nar/gkq854

Experimental method

SOLUTION NMR