Structural basis for the dual RNA-recognition modes of human Tra2-ß RRM.
Nucleic Acids Res
; 39(4): 1538-53, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-20926394
ABSTRACT
Human Transformer2-ß (hTra2-ß) 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-ß specifically binds to two types of RNA sequences [the CAA and (GAA)(2) sequences]. We determined the solution structure of the hTra2-ß 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 ß-sheet surface. We then solved the complex structure of the hTra2-ß 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 ß-sheet surface. Further NMR experiments revealed that the hTra2-ß RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-ß RRM recognizes two types of RNA sequences in different RNA binding modes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Proteínas de Ligação a RNA
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão