Structure of PTB bound to RNA: specific binding and implications for splicing regulation.
The polypyrimidine tract binding protein (PTB) is a 58-kilodalton RNA binding protein involved in multiple aspects of messenger RNA metabolism, including the repression of alternative exons. We have determined the solution structures of the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3 and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA looping when bound to two separated pyrimidine tracts within the same RNA. This leads to structural models for how PTB functions as an alternative-splicing repressor.
Oberstrass
Florian C
FC
Institute for Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology, Zürich, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
Auweter
Sigrid D
SD
Erat
Michèle
M
Hargous
Yann
Y
Henning
Anke
A
Wenter
Philipp
P
Reymond
Luc
L
Amir-Ahmady
Batoul
B
Pitsch
Stefan
S
Black
Douglas L
DL
Allain
Frédéric H-T
FH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000378:metabolism; D009843:Oligoribonucleotides; D038941:Polypyrimidine Tract-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D000072668:Splicing Factor U2AF
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D009843:Oligoribonucleotides; C450006:PTBP1 protein, human; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; D038941:Polypyrimidine Tract-Binding Protein; D012313:RNA