PDBsum entry 1qlc

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protein links
Peptide recognition PDB id
Protein chain
95 a.a. *
* Residue conservation analysis
PDB id:
Name: Peptide recognition
Title: Solution structure of the second pdz domain of postsynaptic density-95
Structure: Postsynaptic density protein 95. Chain: a. Fragment: the second pdz domain. Synonym: psd-95. Engineered: yes
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562
NMR struc: 20 models
Authors: H.Tochio,F.Hung,M.Li,M.Zhang
Key ref:
H.Tochio et al. (2000). Solution structure and backbone dynamics of the second PDZ domain of postsynaptic density-95. J Mol Biol, 295, 225-237. PubMed id: 10623522 DOI: 10.1006/jmbi.1999.3350
25-Aug-99     Release date:   06-Feb-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P31016  (DLG4_RAT) -  Disks large homolog 4
724 a.a.
95 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1006/jmbi.1999.3350 J Mol Biol 295:225-237 (2000)
PubMed id: 10623522  
Solution structure and backbone dynamics of the second PDZ domain of postsynaptic density-95.
H.Tochio, F.Hung, M.Li, D.S.Bredt, M.Zhang.
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.
  Selected figure(s)  
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.
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.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 225-237) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20054121 M.Fiorentini, A.K.Nielsen, O.Kristensen, J.S.Kastrup, and M.Gajhede (2009).
Structure of the first PDZ domain of human PSD-93.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1254-1257.
PDB code: 2wl7
19732061 S.K.Florio, C.Loh, S.M.Huang, A.E.Iwamaye, K.F.Kitto, K.W.Fowler, J.A.Treiberg, J.S.Hayflick, J.M.Walker, C.A.Fairbanks, and Y.Lai (2009).
Disruption of nNOS-PSD95 protein-protein interaction inhibits acute thermal hyperalgesia and chronic mechanical allodynia in rodents.
  Br J Pharmacol, 158, 494-506.  
19585657 Z.N.Gerek, O.Keskin, and S.B.Ozkan (2009).
Identification of specificity and promiscuity of PDZ domain interactions through their dynamic behavior.
  Proteins, 77, 796-811.  
18474209 L.M.Brzustowicz (2008).
NOS1AP in schizophrenia.
  Curr Psychiatry Rep, 10, 158-163.  
18172569 S.S.Tungteakkhun, and P.J.Duerksen-Hughes (2008).
Cellular binding partners of the human papillomavirus E6 protein.
  Arch Virol, 153, 397-408.  
17443799 K.Langnaese, K.Richter, K.H.Smalla, M.Krauss, U.Thomas, G.Wolf, and G.Laube (2007).
Splice-isoform specific immunolocalization of neuronal nitric oxide synthase in mouse and rat brain reveals that the PDZ-complex-building nNOSalpha beta-finger is largely exposed to antibodies.
  Dev Neurobiol, 67, 422-437.  
  16796391 A.Piserchio, M.Spaller, and D.F.Mierke (2006).
Targeting the PDZ domains of molecular scaffolds of transmembrane ion channels.
  AAPS J, 8, E396-E401.  
17018532 C.N.Chi, A.Engström, S.Gianni, M.Larsson, and P.Jemth (2006).
Two conserved residues govern the salt and pH dependencies of the binding reaction of a PDZ domain.
  J Biol Chem, 281, 36811-36818.  
17096593 D.Korkin, F.P.Davis, F.Alber, T.Luong, M.Y.Shen, V.Lucic, M.B.Kennedy, and A.Sali (2006).
Structural modeling of protein interactions by analogy: application to PSD-95.
  PLoS Comput Biol, 2, e153.  
17069616 I.von Ossowski, E.Oksanen, L.von Ossowski, C.Cai, M.Sundberg, A.Goldman, and K.Keinänen (2006).
Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide.
  FEBS J, 273, 5219-5229.
PDB codes: 2awu 2aww 2awx 2g2l
18615145 Y.X.Tao, and R.A.Johns (2006).
PDZ domains at excitatory synapses: potential molecular targets for persistent pain treatment.
  Curr Neuropharmacol, 4, 217-223.  
16146415 B.Xu, N.Wratten, E.I.Charych, S.Buyske, B.L.Firestein, and L.M.Brzustowicz (2005).
Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder.
  PLoS Med, 2, e263.  
15684424 H.Zhou, Y.Xu, Y.Yang, A.Huang, J.Wu, and Y.Shi (2005).
Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr.
  J Biol Chem, 280, 13841-13847.
PDB code: 1t2m
15631993 J.Cao, J.I.Viholainen, C.Dart, H.K.Warwick, M.L.Leyland, and M.J.Courtney (2005).
The PSD95-nNOS interface: a target for inhibition of excitotoxic p38 stress-activated protein kinase activation and cell death.
  J Cell Biol, 168, 117-126.  
15978037 L.C.van den Berk, E.Landi, E.Harmsen, L.Dente, and W.J.Hendriks (2005).
Redox-regulated affinity of the third PDZ domain in the phosphotyrosine phosphatase PTP-BL for cysteine-containing target peptides.
  FEBS J, 272, 3306-3316.  
15929985 L.Wang, A.Piserchio, and D.F.Mierke (2005).
Structural characterization of the intermolecular interactions of synapse-associated protein-97 with the NR2B subunit of N-methyl-D-aspartate receptors.
  J Biol Chem, 280, 26992-26996.
PDB code: 1zok
15123241 A.Piserchio, G.D.Salinas, T.Li, J.Marshall, M.R.Spaller, and D.F.Mierke (2004).
Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide.
  Chem Biol, 11, 469-473.
PDB code: 1rgr
15663004 L.C.van den Berk, M.A.van Ham, M.M.te Lindert, T.Walma, J.Aelen, G.W.Vuister, and W.J.Hendriks (2004).
The interaction of PTP-BL PDZ domains with RIL: an enigmatic role for the RIL LIM domain.
  Mol Biol Rep, 31, 203-215.  
12717014 D.Idiyatullin, I.Nesmelova, V.A.Daragan, and K.H.Mayo (2003).
Comparison of (13)C(alpha)H and (15)NH backbone dynamics in protein GB1.
  Protein Sci, 12, 914-922.  
12444095 G.Birrane, J.Chung, and J.A.Ladias (2003).
Novel mode of ligand recognition by the Erbin PDZ domain.
  J Biol Chem, 278, 1399-1402.
PDB codes: 1mfg 1mfl
12682077 L.L.Parker, J.R.Backstrom, E.Sanders-Bush, and B.H.Shieh (2003).
Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates its interaction with multiple PDZ protein 1.
  J Biol Chem, 278, 21576-21583.  
12853458 M.Fang, Y.X.Tao, F.He, M.Zhang, C.F.Levine, P.Mao, F.Tao, C.L.Chou, S.Sadegh-Nasseri, and R.A.Johns (2003).
Synaptic PDZ domain-mediated protein interactions are disrupted by inhalational anesthetics.
  J Biol Chem, 278, 36669-36675.  
12446668 N.J.Skelton, M.F.Koehler, K.Zobel, W.L.Wong, S.Yeh, M.T.Pisabarro, J.P.Yin, L.A.Lasky, and S.S.Sidhu (2003).
Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain.
  J Biol Chem, 278, 7645-7654.
PDB code: 1n7t
14555997 W.Feng, Y.Shi, M.Li, and M.Zhang (2003).
Tandem PDZ repeats in glutamate receptor-interacting proteins have a novel mode of PDZ domain-mediated target binding.
  Nat Struct Biol, 10, 972-978.
PDB codes: 1p1d 1p1e
11744724 A.Piserchio, M.Pellegrini, S.Mehta, S.M.Blackman, E.P.Garcia, J.Marshall, and D.F.Mierke (2002).
The PDZ1 domain of SAP90. Characterization of structure and binding.
  J Biol Chem, 277, 6967-6973.
PDB code: 1kef
11741967 A.Y.Hung, and M.Sheng (2002).
PDZ domains: structural modules for protein complex assembly.
  J Biol Chem, 277, 5699-5702.  
12359873 E.Schnell, M.Sizemore, S.Karimzadegan, L.Chen, D.S.Bredt, and R.A.Nicoll (2002).
Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number.
  Proc Natl Acad Sci U S A, 99, 13902-13907.  
11723117 F.Imamura, S.Maeda, T.Doi, and Y.Fujiyoshi (2002).
Ligand binding of the second PDZ domain regulates clustering of PSD-95 with the Kv1.4 potassium channel.
  J Biol Chem, 277, 3640-3646.  
11937501 I.A.Lim, D.D.Hall, and J.W.Hell (2002).
Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102.
  J Biol Chem, 277, 21697-21711.  
11283303 M.Sheng, and C.Sala (2001).
PDZ domains and the organization of supramolecular complexes.
  Annu Rev Neurosci, 24, 1.  
11060025 H.Wu, C.Reissner, S.Kuhlendahl, B.Coblentz, S.Reuver, S.Kindler, E.D.Gundelfinger, and C.C.Garner (2000).
Intramolecular interactions regulate SAP97 binding to GKAP.
  EMBO J, 19, 5740-5751.  
10824095 P.Wang, Q.Zhang, H.Tochio, J.S.Fan, and M.Zhang (2000).
Formation of a native-like beta-hairpin finger structure of a peptide from the extended PDZ domain of neuronal nitric oxide synthase in aqueous solution.
  Eur J Biochem, 267, 3116-3122.  
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.