PDBsum entry 4gbq

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protein Protein-protein interface(s) links
Complex (signal transduction/peptide) PDB id
Protein chains
57 a.a. *
12 a.a. *
* Residue conservation analysis
PDB id:
Name: Complex (signal transduction/peptide)
Title: Solution nmr 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, 15 structures
Structure: Grb2. Chain: a. Fragment: n-terminal sh3 domain. Engineered: yes. Sos-1. Chain: b. Fragment: residues 1135 - 1144. Synonym: ac-vpppvpprrr-nh2. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Cell_line: bl21. Cellular_location: cytoplasmic. Gene: potential. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 15 models
Authors: M.Wittekind,C.Mapelli,V.Lee,V.Goldfarb,M.S.Friedrichs, C.A.Meyers,L.Mueller
Key ref:
M.Wittekind et al. (1997). 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. J Mol Biol, 267, 933-952. PubMed id: 9135122 DOI: 10.1006/jmbi.1996.0886
23-Dec-96     Release date:   04-Sep-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q60631  (GRB2_MOUSE) -  Growth factor receptor-bound protein 2
217 a.a.
57 a.a.
Protein chain
Pfam   ArchSchema ?
Q62245  (SOS1_MOUSE) -  Son of sevenless homolog 1
1319 a.a.
11 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)


DOI no: 10.1006/jmbi.1996.0886 J Mol Biol 267:933-952 (1997)
PubMed id: 9135122  
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.
M.Wittekind, C.Mapelli, V.Lee, V.Goldfarb, M.S.Friedrichs, C.A.Meyers, L.Mueller.
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.
  Selected figure(s)  
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.
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 , 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).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 267, 933-952) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21227701 T.Kaneko, S.S.Sidhu, and S.S.Li (2011).
Evolving specificity from variability for protein interaction domains.
  Trends Biochem Sci, 36, 183-190.  
20005866 C.B.McDonald, K.L.Seldeen, B.J.Deegan, V.Bhat, and A.Farooq (2010).
Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control.
  Arch Biochem Biophys, 494, 216-225.  
19921743 C.Rubini, P.Ruzza, M.R.Spaller, G.Siligardi, R.Hussain, D.G.Udugamasooriya, M.Bellanda, S.Mammi, A.Borgogno, A.Calderan, L.Cesaro, A.M.Brunati, and A.Donella-Deana (2010).
Recognition of lysine-rich peptide ligands by murine cortactin SH3 domain: CD, ITC, and NMR studies.
  Biopolymers, 94, 298-306.  
19669081 P.He, W.Wu, H.D.Wang, K.Yang, K.L.Liao, and W.Zhang (2010).
Toward quantitative characterization of the binding profile between the human amphiphysin-1 SH3 domain and its peptide ligands.
  Amino Acids, 38, 1209-1218.  
19323566 C.B.McDonald, K.L.Seldeen, B.J.Deegan, and A.Farooq (2009).
SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner.
  Biochemistry, 48, 4074-4085.  
20064468 J.F.Trempe, C.X.Chen, K.Grenier, E.M.Camacho, G.Kozlov, P.S.McPherson, K.Gehring, and E.A.Fon (2009).
SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination.
  Mol Cell, 36, 1034-1047.
PDB codes: 2knb 3iql
19023120 T.Hou, Z.Xu, W.Zhang, W.A.McLaughlin, D.A.Case, Y.Xu, and W.Wang (2009).
Characterization of domain-peptide interaction interface: a generic structure-based model to decipher the binding specificity of SH3 domains.
  Mol Cell Proteomics, 8, 639-649.  
17355961 M.Brucet, J.Querol-Audí, M.Serra, X.Ramirez-Espain, K.Bertlik, L.Ruiz, J.Lloberas, M.J.Macias, I.Fita, and A.Celada (2007).
Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW Domains.
  J Biol Chem, 282, 14547-14557.
PDB codes: 2o4g 2o4i
17362087 M.R.Yun, N.Mousseau, and P.Derreumaux (2007).
Sampling small-scale and large-scale conformational changes in proteins and molecular complexes.
  J Chem Phys, 126, 105101.  
17765920 Y.He, L.Hicke, and I.Radhakrishnan (2007).
Structural basis for ubiquitin recognition by SH3 domains.
  J Mol Biol, 373, 190-196.
PDB code: 2jt4
16446784 T.Hou, K.Chen, W.A.McLaughlin, B.Lu, and W.Wang (2006).
Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.
  PLoS Comput Biol, 2, e1.  
15880548 L.J.Ball, R.Kühne, J.Schneider-Mergener, and H.Oschkinat (2005).
Recognition of Proline-Rich Motifs by Protein-Protein-Interaction Domains.
  Angew Chem Int Ed Engl, 44, 2852-2869.  
12598123 E.O.Freed (2003).
The HIV-TSG101 interface: recent advances in a budding field.
  Trends Microbiol, 11, 56-59.  
12592015 J.C.Ferreon, and V.J.Hilser (2003).
The effect of the polyproline II (PPII) conformation on the denatured state entropy.
  Protein Sci, 12, 447-457.  
12379843 O.Pornillos, S.L.Alam, D.R.Davis, and W.I.Sundquist (2002).
Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein.
  Nat Struct Biol, 9, 812-817.
PDB codes: 1m4p 1m4q
11500884 G.Tuchscherer, D.Grell, Y.Tatsu, P.Durieux, J.Fernandez-Carneado, B.Hengst, C.Kardinal, and S.Feller (2001).
Targeting Molecular Recognition: Exploring the Dual Role of Functional Pseudoprolines in the Design of SH3 Ligands This work was supported by the Swiss National Science Foundation.
  Angew Chem Int Ed Engl, 40, 2844-2848.  
11353842 S.H.Ong, Y.R.Hadari, N.Gotoh, G.R.Guy, J.Schlessinger, and I.Lax (2001).
Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins.
  Proc Natl Acad Sci U S A, 98, 6074-6079.  
10869177 J.A.Bousquet, C.Garbay, B.P.Roques, and Y.Mély (2000).
Circular dichroic investigation of the native and non-native conformational states of the growth factor receptor-binding protein 2 N-terminal src homology domain 3: effect of binding to a proline-rich peptide from guanine nucleotide exchange factor.
  Biochemistry, 39, 7722-7735.  
10880974 M.Iwadate, E.Nagao, M.P.Williamson, M.Ueki, and T.Asakura (2000).
Structure determination of [Arg8]vasopressin methylenedithioether in dimethylsulfoxide using NMR.
  Eur J Biochem, 267, 4504-4510.  
9422760 D.Dowbenko, S.Spencer, C.Quan, and L.A.Lasky (1998).
Identification of a novel polyproline recognition site in the cytoskeletal associated protein, proline serine threonine phosphatase interacting protein.
  J Biol Chem, 273, 989-996.  
9566119 D.C.Dalgarno, M.C.Botfield, and R.J.Rickles (1997).
SH3 domains and drug design: ligands, structure, and biological function.
  Biopolymers, 43, 383-400.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.