Common mechanism of ligand recognition by group II/III WW domains: redefining their functional classification

• Published in: The Journal of biological chemistry Vol. 279; no. 30; pp. 31833 - 31841
• Main Authors: Kato, Yusuke, Nagata, Koji, Takahashi, Mihoko, Lian, Lubing, Herrero, Juan J, Sudol, Marius, Tanokura, Masaru
• Format: Journal Article
• Language: English
• Published: United States 23-07-2004
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Humans; In Vitro Techniques; Kinetics; Ligands; Models, Molecular; Molecular Sequence Data; NIMA-Interacting Peptidylprolyl Isomerase; Peptidylprolyl Isomerase - chemistry; Peptidylprolyl Isomerase - genetics; Peptidylprolyl Isomerase - metabolism; Proline - chemistry; Protein Structure, Tertiary; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Surface Plasmon Resonance
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M404719200

WW domain is a well known protein module that mediates protein to protein interactions by binding to proline-containing ligands. Based on the ligand predilections, the WW domains have been classified into four major groups. Group II and III WW domains have been reported to bind the proline-leucine and proline-arginine motifs, respectively. In the present study, using surface plasmon resonance technique we have shown that these WW domains have almost indistinguishable ligand preferences and kinetic properties. Hence, we propose that Group II and III WW domains should be joined together as one group (Group II/III). Unlike Group I and IV WW domains, Group II/III WW domains can bind simple polyprolines as well as the proline-leucine and proline-arginine motifs, and they possess two Xaa-proline (where Xaa is any amino acid) binding grooves similar to SH3 domains. Our work assigns Group II and III WW domains to a larger family of polyproline-binding modules and proteins, which includes SH3 domains and profilin. Because polyprolines belong to the most frequently found peptide motifs in several genomes, our study implies the versatile importance of Group II/III WW domains in signaling.