2ERR

NMR Structure of the RNA Binding Domain of Human Fox-1 in Complex with UGCAUGU

Summary for 2ERR

• Entry DOI: 10.2210/pdb2err/pdb
• NMR Information: BMRB: 6895
• Descriptor: UGCAUGU, Ataxin-2-binding protein 1 (2 entities in total)
• Functional Keywords: protein-rna complex, rna binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (By similarity): Q9NWB1
• Total number of polymer chains: 2
• Total formula weight: 14598.32

Authors

Allain, F.H.,Auweter, S.D. (deposition date: 2005-10-25, release date: 2006-01-10, Last modification date: 2024-05-22)

Primary citation

Auweter, S.D.,Fasan, R.,Reymond, L.,Underwood, J.G.,Black, D.L.,Pitsch, S.,Allain, F.H.
Molecular basis of RNA recognition by the human alternative splicing factor Fox-1.
Embo J., 25:163-173, 2006

PubMed Abstract: The Fox-1 protein regulates alternative splicing of tissue-specific exons by binding to GCAUG elements. Here, we report the solution structure of the Fox-1 RNA binding domain (RBD) in complex with UGCAUGU. The last three nucleotides, UGU, are recognized in a canonical way by the four-stranded beta-sheet of the RBD. In contrast, the first four nucleotides, UGCA, are bound by two loops of the protein in an unprecedented manner. Nucleotides U1, G2, and C3 are wrapped around a single phenylalanine, while G2 and A4 form a base-pair. This novel RNA binding site is independent from the beta-sheet binding interface. Surface plasmon resonance analyses were used to quantify the energetic contributions of electrostatic and hydrogen bond interactions to complex formation and support our structural findings. These results demonstrate the unusual molecular mechanism of sequence-specific RNA recognition by Fox-1, which is exceptional in its high affinity for a defined but short sequence element.

PubMed: 16362037
DOI: 10.1038/sj.emboj.7600918

Experimental method

SOLUTION NMR