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Signaling protein
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PDB id
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1oy2
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Contents |
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* Residue conservation analysis
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DOI no:
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Structure
11:905-913
(2003)
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PubMed id:
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Coupling of folding and binding in the PTB domain of the signaling protein Shc.
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A.Farooq,
L.Zeng,
K.S.Yan,
K.S.Ravichandran,
M.M.Zhou.
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ABSTRACT
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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.
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Selected figure(s)
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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).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
905-913)
copyright 2003.
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Figure was
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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Arch Biochem Biophys, 494,
216-225.
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M.Gertz,
and
C.Steegborn
(2010).
The Lifespan-regulator p66Shc in mitochondria: redox enzyme or redox sensor?
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Antioxid Redox Signal, 13,
1417-1428.
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M.J.Smith,
W.R.Hardy,
G.Y.Li,
M.Goudreault,
S.Hersch,
P.Metalnikov,
A.Starostine,
T.Pawson,
and
M.Ikura
(2010).
The PTB domain of ShcA couples receptor activation to the cytoskeletal regulator IQGAP1.
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EMBO J, 29,
884-896.
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M.Gertz,
F.Fischer,
D.Wolters,
and
C.Steegborn
(2008).
Activation of the lifespan regulator p66Shc through reversible disulfide bond formation.
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Proc Natl Acad Sci U S A, 105,
5705-5709.
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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.
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Protein Sci, 16,
1223-1229.
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PDB code:
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P.Aloy,
and
R.B.Russell
(2006).
Structural systems biology: modelling protein interactions.
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Nat Rev Mol Cell Biol, 7,
188-197.
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A.Ventura,
M.Maccarana,
V.A.Raker,
and
P.G.Pelicci
(2004).
A cryptic targeting signal induces isoform-specific localization of p46Shc to mitochondria.
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J Biol Chem, 279,
2299-2306.
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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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