1k4u

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1k4u

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Solution structure of the C-terminal SH3 domain of p67phox complexed with the C-terminal tail region of p47phox

Contents

Overview

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).

Disease

Known diseases associated with this structure: Chronic granulomatous disease due to deficiency of NCF-1 OMIM:[608512], Chronic granulomatous disease due to deficiency of NCF-2 OMIM:[608515]

About this Structure

1K4U is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p., Kami K, Takeya R, Sumimoto H, Kohda D, EMBO J. 2002 Aug 15;21(16):4268-76. PMID:12169629

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