Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein.
The Sex-lethal (Sxl) protein of Drosophila melanogaster regulates alternative splicing of the transformer (tra) messenger RNA precursor by binding to the tra polypyrimidine tract during the sex-determination process. The crystal structure has now been determined at 2.6 A resolution of the complex formed between two tandemly arranged RNA-binding domains of the Sxl protein and a 12-nucleotide, single-stranded RNA derived from the tra polypyrimidine tract. The two RNA-binding domains have their beta-sheet platforms facing each other to form a V-shaped cleft. The RNA is characteristically extended and bound in this cleft, where the UGUUUUUUU sequence is specifically recognized by the protein. This structure offers the first insight, to our knowledge, into how a protein binds specifically to a cognate RNA without any intramolecular base-pairing.
Handa
N
N
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan.
Nureki
O
O
Kurimoto
K
K
Kim
I
I
Sakamoto
H
H
Shimura
Y
Y
Muto
Y
Y
Yokoyama
S
S
D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004926:Escherichia coli; D007301:Insect Hormones / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011743:Pyrimidines / Q000737:chemistry; D012322:RNA Precursors / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D029721:Drosophila Proteins; D007301:Insect Hormones; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011743:Pyrimidines; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C067777:Sxl protein, Drosophila; C097162:Tra protein, Drosophila