Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67phox, Grb2 and Pex13p

Keiichiro Kami, Ryu Takeya, Hideki Sumimoto, Daisuke Kohda

    Research output: Contribution to journalArticlepeer-review

    143 Citations (Scopus)

    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 p47phox, binds to the C-terminal SH3 domain from p67phox. We applied the NMR cross-saturation method to locate the interaction sites for the non-PxxP peptides on their cognate SH3 domains from p67phox, Grb2 and Pex13p. The binding site of the Grb2 SH3 partially overlapped the conventional PxxP-binding site, whereas those of p67phox and Pex13p SH3s are located in different surface regions. The non-PxxP peptide from p47phox binds to the p67phox 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 p67phox SH3 in a compact helix-turn-helix structure (PDB entry 1K4U).

    Original languageEnglish
    Pages (from-to)4268-4276
    Number of pages9
    JournalEMBO Journal
    Volume21
    Issue number16
    DOIs
    Publication statusPublished - Aug 15 2002

    All Science Journal Classification (ASJC) codes

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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