PDBsum entry 1k4u

Hormone/growth factor

PDB id: 1k4u

Contents

Protein chains

62 a.a. *

32 a.a. *

* Residue conservation analysis

PDB id:

1k4u

Name:

Hormone/growth factor

Title:

Solution structure of thE C-terminal sh3 domain of p67phox complexed with thE C-terminal tail region of p47phox

Structure:

Phagocyte NADPH oxidase subunit p67phox. Chain: s. Fragment: c-terminal sh3 domain (residues 455-516). Synonym: neutrophil cytosol factor 2. Engineered: yes. Mutation: yes. Phagocyte NADPH oxidase subunit p47phox. Chain: p. Fragment: tail peptide (residues 359-390).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ncf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: ncf1.

NMR struc:

22 models

Authors:

K.Kami,R.Takeya,H.Sumimoto,D.Kohda

Key ref:

K.Kami et al. (2002). Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p. EMBO J, 21, 4268-4276. PubMed id: 12169629 DOI: 10.1093/emboj/cdf428

Date:

08-Oct-01 Release date: 08-Apr-02

Protein chain

P19878  (NCF2_HUMAN) -  Neutrophil cytosol factor 2 from Homo sapiens

Seq: 526 a.a.

Struc: 62 a.a.*

Protein chain

P14598  (NCF1_HUMAN) -  Neutrophil cytosol factor 1 from Homo sapiens

Seq: 390 a.a.

Struc: 32 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1093/emboj/cdf428

EMBO J 21:4268-4276 (2002)

PubMed id: 12169629

Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p.

K.Kami, R.Takeya, H.Sumimoto, D.Kohda.

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).

Selected figure(s)

Figure 4.
Figure 4 Summary of the binding sites on three SH3 domains for peptides lacking a PxxP motif. The three SH3 domains from p67^phox, Grb2 and Pexp13p accommodate the cognate non-PxxP peptides with different regions on the molecular surfaces. The SLP-76 peptide-binding site on the Grb2 SH3(C) domain partially overlaps the conventional PxxP motif-binding site.

Figure 5.
Figure 5 Structure of the complex of the p67^phox SH3(C) and the p47^phox tail peptide. (A) Overlay of the 22 NMR structures. The residues used for superimposing the different structures are colored blue (SH3) and red (the tail peptide), and the other residues are in gray. Residue numbers of the p47^phox tail peptide are labeled with a prime ('). (B) Ribbon representation of the lowest energy structure. The -strands of the p67^phox SH3(C) are colored blue: 1, residues 460−463; 2, 483−491; 3, 494−498; 4, 503−506; and the 3[10]-helix is colored green: residues 508−510. The PxxP motif and the two -helices of the p47^phox tail peptide are drawn in red and orange, respectively. Side chains located within the binding interface are shown in pink (SH3) and in yellow (the tail peptide). (C) The same structure viewed from a different angle. The side chains of Leu375', Lys383' and Leu386', colored yellow, fill the space between the two -helices. The positions of the three SH3 loops are shown.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 4268-4276) copyright 2002.

Figures were selected by the author.