 |
PDBsum entry 1k4u
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hormone/growth factor
|
PDB id
|
|
|
|
1k4u
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Diverse recognition of non-Pxxp peptide ligands by the sh3 domains from p67(phox), Grb2 and pex13p.
|
|
|
Authors
|
|
K.Kami,
R.Takeya,
H.Sumimoto,
D.Kohda.
|
|
|
Ref.
|
|
EMBO J, 2002,
21,
4268-4276.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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).
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
