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PDBsum entry 3lny
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Signaling protein/signaling protein
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PDB id
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3lny
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References listed in PDB file
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Key reference
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Title
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Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second pdz domain of protein tyrosine phosphatase 1e.
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Authors
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J.Zhang,
P.J.Sapienza,
H.Ke,
A.Chang,
S.R.Hengel,
H.Wang,
G.N.Phillips,
A.L.Lee.
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Ref.
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Biochemistry, 2010,
49,
9280-9291.
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PubMed id
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Abstract
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PDZ (PSD95/Discs large/ZO-1) domains are ubiquitous protein interaction motifs
found in scaffolding proteins involved in signal transduction. Despite the fact
that many PDZ domains show a limited tendency to undergo structural change, the
PDZ family has been associated with long-range communication and allostery. One
of the PDZ domains studied most in terms of structure and biophysical properties
is the second PDZ ("PDZ2") domain from protein tyrosine phosphatase 1E
(PTP1E, also known as PTPL1). Previously, we showed through NMR relaxation
studies that binding of the RA-GEF2 C-terminal peptide substrate results in
long-range propagation of side-chain dynamic changes in human PDZ2 [Fuentes, E.
J., et al. (2004) J. Mol. Biol. 335, 1105-1115]. Here, we present the first
X-ray crystal structures of PDZ2 in the absence and presence of RA-GEF2 ligand,
determined to resolutions of 1.65 and 1.3 Å, respectively. These structures
deviate somewhat from previously determined NMR structures and indicate that
very minor structural changes in PDZ2 accompany peptide binding. NMR residual
dipolar couplings confirm the crystal structures to be accurate models of the
time-averaged atomic coordinates of PDZ2. The impact on side-chain dynamics was
further tested with a C-terminal peptide from APC, which showed results nearly
identical to those of RA-GEF2. Thus, allosteric transmission in PDZ2 induced by
peptide binding is conveyed purely and robustly by dynamics. (15)N relaxation
dispersion measurements did not detect appreciable populations of a kinetic
structural intermediate. Collectively, for ligand binding to PDZ2, these data
support a lock-and-key binding model from a structural perspective and an
allosteric model from a dynamical perspective, which together suggest a complex
energy landscape for functional transitions within the ensemble.
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