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207 a.a.
Key reference
DOI no: 10.1016/S0969-2126(03)00134-5 Structure 11:905-913 (2003) PubMed id: 12906822
Coupling of folding and binding in the PTB domain of the signaling protein Shc. A.Farooq, L.Zeng, K.S.Yan, K.S.Ravichandran, M.M.Zhou. ABSTRACT
The notion that certain proteins lack intrinsic globular structure under physiological conditions and that the attainment of fully folded structure only occurs upon the binding of target molecules has been recently gaining popularity. We report here the solution structure of the PTB domain of the signaling protein Shc in the free form. Comparison of this structure with that of the complex form, obtained previously with a phosphopeptide ligand, reveals that the Shc PTB domain is structurally disordered in the free form, particularly around the regions constituting the peptide binding pocket. The binding of the ligand appears to reorganize this pocket through local folding events triggering a conformational switch between the free and the complex forms.
Selected figure(s)
Figure 3.
Figure 3. Comparison of the Peptide Binding Pocket in the Free and Complex Forms of the Shc PTB Domain (Residues 39-200)Key protein residues such as R67, R175, I194, and F198 in the Shc PTB domain that line the peptide binding pocket are shown. Shown are key peptide residues at positions pY( -3) and pY( -5), and pY (phosphotyrosine) in the TrkA phosphopeptide that directly interact with the protein. Also shown are close-up ribbon views of the peptide binding pocket in the free form (A) and the complex form (B), and surface potential views of the peptide binding pocket in the free form (C) and the complex form (D).The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 905-913) copyright 2003. Figure was selected by an automated process.
Literature references that cite this PDB file's key reference
PubMed id Reference
18413607 M.Gertz, F.Fischer, D.Wolters, and C.Steegborn (2008).
Activation of the lifespan regulator p66Shc through reversible disulfide bond formation.Proc Natl Acad Sci U S A, 105, 5705-5709.
17473008 C.J.McCleverty, D.C.Lin, and R.C.Liddington (2007).
Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions.Protein Sci, 16, 1223-1229.
PDB code: 1wvh
16496021 P.Aloy, and R.B.Russell (2006).
Structural systems biology: modelling protein interactions.Nat Rev Mol Cell Biol, 7, 188-197.
14573619 A.Ventura, M.Maccarana, V.A.Raker, and P.G.Pelicci (2004).
A cryptic targeting signal induces isoform-specific localization of p46Shc to mitochondria.J Biol Chem, 279, 2299-2306. 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 code is shown on the right.
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