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PDBsum entry 4gbq
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Complex (signal transduction/peptide)
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PDB id
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4gbq
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of the grb2 n-Terminal sh3 domain complexed with a ten-Residue peptide derived from sos: direct refinement against noes, J-Couplings and 1h and 13c chemical shifts.
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Authors
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M.Wittekind,
C.Mapelli,
V.Lee,
V.Goldfarb,
M.S.Friedrichs,
C.A.Meyers,
L.Mueller.
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Ref.
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J Mol Biol, 1997,
267,
933-952.
[DOI no: ]
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PubMed id
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Abstract
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Refined ensembles of solution structures have been calculated for the N-terminal
SH3 domain of Grb2 (N-SH3) complexed with the ac-VPPPVPPRRR-nh2 peptide derived
from residues 1135 to 1144 of the mouse SOS-1 sequence. NMR spectra obtained
from different combinations of both 13C-15N-labeled and unlabeled N-SH3 and SOS
peptide fragment were used to obtain stereo-assignments for pro-chiral groups of
the peptide, angle restraints via heteronuclear coupling constants, and complete
1H, 13C, and 15N resonance assignments for both molecules. One ensemble of
structures was calculated using conventional methods while a second ensemble was
generated by including additional direct refinements against both 1H and
13C(alpha)/13C(beta) chemical shifts. In both ensembles, the protein:peptide
interface is highly resolved, reflecting the inclusion of 110 inter-molecular
nuclear Overhauser enhancement (NOE) distance restraints. The first and second
peptide-binding sub-sites of N-SH3 interact with structurally well-defined
portions of the peptide. These interactions include hydrogen bonds and extensive
hydrophobic contacts. In the third highly acidic sub-site, the conformation of
the peptide Arg8 side-chain is partially ordered by a set of NOE restraints to
the Trp36 ring protons. Overall, several lines of evidence point to dynamical
averaging of peptide and N-SH3 side-chain conformations in the third subsite.
These conformations are characterized by transient charge stabilized hydrogen
bond interactions between the peptide arginine side-chain hydrogen bond donors
and either single, or possibly multiple, acceptor(s) in the third
peptide-binding sub-site.
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Figure 6.
Figure 6. Phi/Psi plots for N-SH3 and the SOS-E pep-
tide in the minimized average
hSA
CS
i
N-SH3:SOS-E
complex structure. Glycine residues are denoted by x
and non-glycines with &. A, Phi and psi angle values
are plotted for N-SH3 residues 1 to 26, 36 to 55. The dis-
ordered loop comprised of N-SH3 residues 27 to 35 is
omitted for clarity. B, Similar plot of SOS-E residues 1
to 10.
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Figure 8.
Figure 8. Stereo view of the back-
bone atoms of N-SH3 residues Ala5
to Asp23 and Lys50 to Ile53. The
Figure shows the SH3 conserved
``AXD'' sequence (Ala5 to
Phe9), the variable RT-loop (resi-
dues Lys10 to Ser18) including the
3 10 helix-like turn at Ala13 to
Glu16, the type II turn at the SH3
conserved ``RGD'' loop (Arg21 to
Asp23), and the conserved 310 helix
(Lys50 to Ile53). Backbone (N, C
a
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C) atoms (gray); HN (light blue,
unprotected from solvent exchange;
blue, protected from solvent
exchange); O (pink, non-H-bond
acceptor; red, H-bond acceptor);
side-chain carbon atoms (white);
side-chain oxygen atoms (magenta).
The side-chains of residues that
participate in H-bonds (Asp8, Ser18, and Asp23) are shown (see the text). H-bonds are depicted as colored broken
lines: included in the structure calculations as restraints (green); not included as restraints but amide proton donor
protected from solvent exchange and H-bond observed in at least 75% of the chemical shift refined structures (yel-
low); same as yellow but amide proton donor not protected from solvent exchange (white). This Figure was made
with the program INSIGHTII (Molecular Simulations, San Diego CA).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
267,
933-952)
copyright 1997.
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Secondary reference #1
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Title
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Orientation of peptide fragments from sos proteins bound to the n-Terminal sh3 domain of grb2 determined by nmr spectroscopy.
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Authors
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M.Wittekind,
C.Mapelli,
B.T.Farmer,
K.L.Suen,
V.Goldfarb,
J.Tsao,
T.Lavoie,
M.Barbacid,
C.A.Meyers,
L.Mueller.
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Ref.
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Biochemistry, 1994,
33,
13531-13539.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Molecular cloning of the mouse grb2 gene: differential interaction of the grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors.
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Authors
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K.L.Suen,
X.R.Bustelo,
T.Pawson,
M.Barbacid.
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Ref.
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Mol Cell Biol, 1993,
13,
5500-5512.
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PubMed id
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Secondary reference #3
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Title
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Identification of murine homologues of the drosophila son of sevenless gene: potential activators of ras.
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Authors
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D.Bowtell,
P.Fu,
M.Simon,
P.Senior.
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Ref.
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Proc Natl Acad Sci U S A, 1992,
89,
6511-6515.
[DOI no: ]
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PubMed id
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