 |
PDBsum entry 1oeb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Protein binding
|
PDB id
|
|
|
|
1oeb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for sh3 domain-Mediated high-Affinity binding between mona/gads and slp-76.
|
|
|
Authors
|
|
M.Harkiolaki,
M.Lewitzky,
R.J.Gilbert,
E.Y.Jones,
R.P.Bourette,
G.Mouchiroud,
H.Sondermann,
I.Moarefi,
S.M.Feller.
|
|
|
Ref.
|
|
EMBO J, 2003,
22,
2571-2582.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
SH3 domains are protein recognition modules within many adaptors and enzymes.
With more than 500 SH3 domains in the human genome, binding selectivity is a key
issue in understanding the molecular basis of SH3 domain interactions. The
Grb2-like adaptor protein Mona/Gads associates stably with the T-cell receptor
signal transducer SLP-76. The crystal structure of a complex between the
C-terminal SH3 domain (SH3C) of Mona/Gads and a SLP-76 peptide has now been
solved to 1.7 A. The peptide lacks the canonical SH3 domain binding motif
P-x-x-P and does not form a frequently observed poly-proline type II helix.
Instead, it adopts a clamp-like shape around the circumfence of the SH3C
beta-barrel. The central R-x-x-K motif of the peptide forms a 3(10) helix and
inserts into a negatively charged double pocket on the SH3C while several other
residues complement binding through hydrophobic interactions, creating a short
linear SH3C binding epitope of uniquely high affinity. Interestingly, the SH3C
displays ion-dependent dimerization in the crystal and in solution, suggesting a
novel mechanism for the regulation of SH3 domain functions.
|
|
|
|
|
|
|
|
Figure 3.
Figure 3 Two views of the Mona/Gads SH3C structure in complex
with the 13 amino acid SLP-76 peptide (P2).  -strands
are coloured blue and 3[10] helices are shown in orange. (A)
View looking down the length of the -barrel.
(B) View rotated by 90° on the vertical axis.
|
|
Figure 8.
Figure 8 Ribbon representations of the Grb2 SH3C and Mona/Gads
SH3C domains with areas involved in molecular docking of an
SLP-76 peptide coloured blue. (A) Grb2 SH3C–peptide
interactions as previously defined by NMR experiments (Kami et
al., 2002). (B) Mona/Gads SH3C–peptide contacts present in the
crystal structure.
|
|
|
|
|
|
The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2003,
22,
2571-2582)
copyright 2003.
|
|
|
|
|
|
|
