Characterization of the interactions between PDZ domains of the protein-tyrosine phosphatase PTPL1 and the carboxyl-terminal tail of Fas.
The intracellular protein-tyrosine phosphatase PTPL1 has five PDZ domains and one of them, PDZ 2, has previously been shown to interact with the C-terminal tail of Fas, a member of the tumor necrosis factor receptor family. Using a peptide binding assay, we show that not only PDZ 2 but also PDZ 4 of PTPL1 interacts with high affinity with peptides derived from the C terminus of Fas. The five most C-terminal amino acid residues of Fas influence the affinity of the interaction. Whereas the glutamine and isoleucine residues in the 4th and 5th positions from the C terminus affect the interaction in a negative and positive manner, respectively, the three C-terminal amino acid residues (SLV) are necessary and sufficient for a high affinity interaction to occur. Both the carboxyl group and side chain of the valine residue at the C terminus of Fas are essential, and the leucine and serine residues in the 2nd and 3rd positions, respectively, from the C terminus are important for the interactions with PDZ 2 and PDZ 4 of PTPL1.
Saras
J
J
Ludwig Institute for Cancer Research, Box 595, Biomedical Centre, S-751 24 Uppsala, Sweden. Jan.Saras@LICR.uu.S.E.
Engström
U
U
Góñez
L J
LJ
Heldin
C H
CH
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D019014:fas Receptor / Q000737:chemistry*
D010455:Peptides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019014:fas Receptor; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases