Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP.
The essential splicing factors SF1 and U2AF play an important role in the recognition of the pre-mRNA 3' splice site during early spliceosome assembly. The structure of the C-terminal RRM (RRM3) of human U2AF(65) complexed to an N-terminal peptide of SF1 reveals an extended negatively charged helix A and an additional helix C. Helix C shields the potential RNA binding surface. SF1 binds to the opposite, helical face of RRM3. It inserts a conserved tryptophan into a hydrophobic pocket between helices A and B in a way that strikingly resembles part of the molecular interface in the U2AF heterodimer. This molecular recognition establishes a paradigm for protein binding by a subfamily of noncanonical RRMs.
Selenko
Philipp
P
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Gregorovic
Goran
G
Sprangers
Remco
R
Stier
Gunter
G
Rhani
Zakaria
Z
Krämer
Angela
A
Sattler
Michael
M
D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D009687:Nuclear Proteins; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000072668:Splicing Factor U2AF; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C107467:SF1 protein, human; D000072668:Splicing Factor U2AF; D014157:Transcription Factors; C000607494:U2AF2 protein, human