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PDBsum entry 1qlc
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Peptide recognition
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PDB id
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1qlc
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure and backbone dynamics of the second pdz domain of postsynaptic density-95.
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Authors
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H.Tochio,
F.Hung,
M.Li,
D.S.Bredt,
M.Zhang.
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Ref.
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J Mol Biol, 2000,
295,
225-237.
[DOI no: ]
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PubMed id
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Abstract
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The second PDZ domain of postsynaptic density-95 (PSD-95 PDZ2) plays a critical
role in coupling N-methyl-D-aspartate receptors to neuronal nitric oxide
synthase (nNOS). In this work, the solution structure of PSD-95 PDZ2 was
determined to high resolution by NMR spectroscopy. The structure of PSD-95 PDZ2
was compared in detail with that of alpha1-syntrophin PDZ domain, as the PDZ
domains share similar target interaction properties. The interaction of the
PSD-95 PDZ2 with a carboxyl-terminal peptide derived from a cytoplasmic protein
CAPON was studied by NMR titration experiments. Complex formation between PSD-95
PDZ2 and the nNOS PDZ was modelled on the basis of the crystal structure of the
alpha1-syntrophin PDZ/nNOS PDZ dimer. We found that the prolonged loop
connecting the betaB and betaC strands of PSD-95 PDZ2 is likely to play a role
in both the binding of the carboxyl-terminal peptide and the nNOS beta-finger.
Finally, the backbone dynamics of the PSD-95 PDZ2 in the absence of bound
peptide were studied using a model-free approach. The "GLGF"-loop and
the loop connecting alphaB and betaF of the protein display some degree of
flexibility in solution. The rest of the protein is rigid and lacks detectable
slow time-scale (microseconds to milliseconds) motions. In particular, the loop
connecting betaB and betaC loop adopts a well-defined, rigid structure in
solution. It appears that the loop adopts a pre-aligned conformation for the PDZ
domain to interact with its targets.
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Figure 2.
Figure 2. Stereoview showing the best-fit superposition of the backbone atoms (N, C
a
, and C0) of the final 20 struc-
tures of PSD-95 PDZ2. The structures are superimposed against the average structure using the residues 158-246. The
program MOLMOL (Koradi et al., 1996) was used to generate the Figure.
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Figure 6.
Figure 6. Model of the PSD-95
PDZ2 and the nNOS PDZ complex.
In this model, PSD-95 PDZ2
(green) is superimposed on the a1-
syntrophin PDZ domain (red)
(Hillier et al., 1999). The nNOS PDZ
domain is shown in blue. The
Figure was generated using MOL-
SCRIPT and Raster3D.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
295,
225-237)
copyright 2000.
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