1. Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p.
- Author
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Kami K, Takeya R, Sumimoto H, and Kohda D
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Binding Sites, CSK Tyrosine-Protein Kinase, Escherichia coli, GRB2 Adaptor Protein, Humans, Ligands, Models, Molecular, Molecular Sequence Data, Mutation, NADPH Oxidases, Peptides, Cyclic metabolism, Protein Binding, Protein Conformation, Protein-Tyrosine Kinases metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Saccharomyces cerevisiae Proteins metabolism, Sequence Deletion, src-Family Kinases, Adaptor Proteins, Signal Transducing, Membrane Proteins metabolism, Phosphoproteins metabolism, Proteins metabolism, src Homology Domains physiology
- Abstract
The basic function of the Src homology 3 (SH3) domain is considered to be binding to proline-rich sequences containing a PxxP motif. Recently, many SH3 domains, including those from Grb2 and Pex13p, were reported to bind sequences lacking a PxxP motif. We report here that the 22 residue peptide lacking a PxxP motif, derived from p47(phox), binds to the C-terminal SH3 domain from p67(phox). We applied the NMR cross-saturation method to locate the interaction sites for the non-PxxP peptides on their cognate SH3 domains from p67(phox), Grb2 and Pex13p. The binding site of the Grb2 SH3 partially overlapped the conventional PxxP-binding site, whereas those of p67(phox) and Pex13p SH3s are located in different surface regions. The non-PxxP peptide from p47(phox) binds to the p67(phox) SH3 more tightly when it extends to the N-terminus to include a typical PxxP motif, which enabled the structure determination of the complex, to reveal that the non-PxxP peptide segment interacted with the p67(phox) SH3 in a compact helix-turn-helix structure (PDB entry 1K4U).
- Published
- 2002
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