2H46
Native domain-swapped dimer crystal structure of the Grb2 SH2 domain
Summary for 2H46
| Entry DOI | 10.2210/pdb2h46/pdb |
| Descriptor | Growth Receptor Binding Protein 2, GLYCEROL (3 entities in total) |
| Functional Keywords | helix-sheet-helix, hormone-growth factor complex, hormone/growth factor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13779.56 |
| Authors | Benfield, A.P.,Martin, S.F.,Whiddon, B.B. (deposition date: 2006-05-23, release date: 2006-06-06, Last modification date: 2024-02-14) |
| Primary citation | Benfield, A.P.,Whiddon, B.B.,Clements, J.H.,Martin, S.F. Structural and energetic aspects of Grb2-SH2 domain-swapping. Arch.Biochem.Biophys., 462:47-53, 2007 Cited by PubMed Abstract: The SH2 domain of growth factor receptor-bound protein 2 (Grb2) has been the focus of numerous studies, primarily because of the important roles it plays in signal transduction. More recently, it has emerged as a useful protein to study the consequences of ligand preorganization upon energetics and structure in protein-ligand interactions. The Grb2-SH2 domain is known to form a domain-swapped dimer, and as part of our investigations toward correlating structure and energetics in biological systems, we examined the effects that domain-swapping dimerization of the Grb2-SH2 domain had upon ligand binding affinities. Isothermal titration calorimetry was performed using Grb2-SH2 in both its monomeric and domain-swapped dimeric forms and a phosphorylated tripeptide AcNH-pTyr-Val-Asn-NH(2) that is similar to the Shc sequence recognized by Grb2-SH2 in vivo. The two binding sites of domain-swapped dimer exhibited a 4- and a 13-fold reduction in ligand affinity compared to monomer. Crystal structures of peptide-bound and uncomplexed forms of Grb2-SH2 domain-swapped dimer were obtained and reveal that the orientation of residues V122, V123, and R142 may influence the conformation of W121, an amino acid that is believed to play an important role in Grb2-SH2 ligand sequence specificity. These findings suggest that domain-swapping of Grb2-SH2 not only results in a lower affinity for a Shc-derived ligand, but it may also affect ligand specificity. PubMed: 17466257DOI: 10.1016/j.abb.2007.03.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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