PDBsum entry 1iu2

Go to PDB code: 
protein links
Neuropeptide PDB id
Protein chain
91 a.a. *
* Residue conservation analysis
PDB id:
Name: Neuropeptide
Title: The first pdz domain of psd-95
Structure: Psd-95. Chain: a. Fragment: pdz1 domain. Synonym: presynaptic density protein 95. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562
NMR struc: 50 models
Authors: J.-F.Long,H.Tochio,P.Wang,C.Sala,M.Niethammer,M.Sheng, M.Zhang
Key ref:
J.F.Long et al. (2003). Supramodular structure and synergistic target binding of the N-terminal tandem PDZ domains of PSD-95. J Mol Biol, 327, 203-214. PubMed id: 12614619 DOI: 10.1016/S0022-2836(03)00113-X
19-Feb-02     Release date:   11-Mar-03    
Go to PROCHECK summary

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


DOI no: 10.1016/S0022-2836(03)00113-X J Mol Biol 327:203-214 (2003)
PubMed id: 12614619  
Supramodular structure and synergistic target binding of the N-terminal tandem PDZ domains of PSD-95.
J.F.Long, H.Tochio, P.Wang, J.S.Fan, C.Sala, M.Niethammer, M.Sheng, M.Zhang.
PDZ domain proteins play critical roles in binding, clustering and subcellular targeting of membrane receptors and ion channels. PDZ domains in multi-PDZ proteins often are arranged in groups with highly conserved spacing and intervening sequences; however, the functional significance of such tandem arrangements of PDZs is unclear. We have solved the three-dimensional structure of the first two PDZ domains of postsynaptic density protein-95 (PSD-95 PDZ1 and PDZ2), which are closely linked to each other in the PSD-95 family of scaffold proteins. The two PDZs have limited freedom of rotation and their C-terminal peptide-binding grooves are aligned with each other with an orientation preference for binding to pairs of C termini extending in the same direction. Increasing the spacing between PDZ1 and PDZ2 resulted in decreased binding between PDZ12 and its dimeric targets. The same mutation impaired the functional ability of PSD-95 to cluster Kv1.4 potassium channels in heterologous cells. The data presented provide a molecular basis for preferential binding of PSD-95 to multimeric membrane proteins with appropriate C-terminal sequences.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of PSD-95 PDZ1 determined by NMR spectroscopy. (A) Stereoview showing the best-fit superposition of the backbone atoms (N, C^a, and C') of the final 20 structures of PSD-95 PDZ1. The structures are superimposed against the average structure using the residues 64-148. The structural statistics are summarized in Table 1. (B) Ribbon diagram presentation of PSD-95 PDZ1. The secondary structure elements are labelled following the scheme used in the crystal structure of PSD-95 PDZ3. [7] (C) Comparison of the 3D structures of PDZ1 and PDZ2 of PSD-95. The backbone traces (N, C^a, and C') of PDZ1 (gold) and PDZ2 (yellow) are superimposed. The two structures were fit to each other by excluding the GLGF-loop, bB/bC loop and the two termini. The rmsd between the backbones of the two PDZ domains is 1.35 Å.
Figure 5.
Figure 5. Functional role of conformation-restrained tandem PDZ repeats in PSD-95. (A) Extending the PDZ12 linker by introducing flexible amino acid residues reduces the size of the Kv1.4 channel clusters mediated by N-PDZ12. Myc-tagged constructs N-PDZ1-2 wild-type (N-PDZ12), the deletion mutant of N-PDZ12 (N-PDZ12Del) and the insertion mutant of N-PDZ12 (N-PDZ1-2Ins) were co-transfected in COS7 cells with potassium channel subunit Kv1.4. Cells cotransfected with different constructs, as indicated, were fixed two days after transfection and stained with Kv1.4 antibodies to visualize the potassium channel clusters. The schematics of the deletions and insertion mutations used in this study are shown. Insets show higher-magnification views of Kv1.4 clusters. (B) Frequency distribution (left) and mean values (right) of Kv1.4 cluster areas mediated by N-PDZ12, N-PDZ12(Del) and N-PDZ12(Ins), measured from at least ten cells for each construct. The scale bars represent 5 µm or 15 µm for the insets. An asterisk (*) indicates significance at p <0.01 in an unpaired, two-tailed Student's t-test.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 203-214) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21422294 B.Balana, I.Maslennikov, W.Kwiatkowski, K.M.Stern, L.Bahima, S.Choe, and P.A.Slesinger (2011).
Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27.
  Proc Natl Acad Sci U S A, 108, 5831-5836.
PDB codes: 3qdo 3qe1 3qgl
21186349 M.Sainlos, C.Tigaret, C.Poujol, N.B.Olivier, L.Bard, C.Breillat, K.Thiolon, D.Choquet, and B.Imperiali (2011).
Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization.
  Nat Chem Biol, 7, 81-91.
PDB code: 3gsl
20531955 C.A.Brown, and K.S.Brown (2010).
Validation of coevolving residue algorithms via pipeline sensitivity analysis: ELSC and OMES and ZNMI, oh my!
  PLoS One, 5, e10779.  
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
  20042479 M.Zheng, H.Cheng, I.Banerjee, and J.Chen (2010).
ALP/Enigma PDZ-LIM domain proteins in the heart.
  J Mol Cell Biol, 2, 96.  
20715264 W.S.Iskenderian-Epps, and B.Imperiali (2010).
Modulation of Shank3 PDZ domain ligand-binding affinity by dimerization.
  Chembiochem, 11, 1979-1984.  
  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
19153575 W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.
  Nat Rev Neurosci, 10, 87-99.  
17828302 S.H.Chung, R.S.Weiss, K.K.Frese, B.V.Prasad, and R.T.Javier (2008).
Functionally distinct monomers and trimers produced by a viral oncoprotein.
  Oncogene, 27, 1412-1420.  
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
18799665 X.Chen, C.A.Winters, and T.S.Reese (2008).
Life inside a thin section: tomography.
  J Neurosci, 28, 9321-9327.  
17334360 B.A.Jordan, B.D.Fernholz, L.Khatri, and E.B.Ziff (2007).
Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons.
  Nat Neurosci, 10, 427-435.  
17666528 E.Magidovich, I.Orr, D.Fass, U.Abdu, and O.Yifrach (2007).
Intrinsic disorder in the C-terminal domain of the Shaker voltage-activated K+ channel modulates its interaction with scaffold proteins.
  Proc Natl Acad Sci U S A, 104, 13022-13027.  
18082612 H.Wu, W.Feng, J.Chen, L.N.Chan, S.Huang, and M.Zhang (2007).
PDZ domains of Par-3 as potential phosphoinositide signaling integrators.
  Mol Cell, 28, 886-898.
PDB code: 2ogp
17914463 L.Pan, H.Wu, C.Shen, Y.Shi, W.Jin, J.Xia, and M.Zhang (2007).
Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.
  EMBO J, 26, 4576-4587.
PDB code: 2pku
17656366 M.D.Jennings, R.T.Blankley, M.Baron, A.P.Golovanov, and J.M.Avis (2007).
Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.
  J Biol Chem, 282, 29032-29042.
PDB code: 2jmf
17828261 M.L.Lunn, R.Nassirpour, C.Arrabit, J.Tan, I.McLeod, C.M.Arias, P.E.Sawchenko, J.R.Yates, and P.A.Slesinger (2007).
A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction.
  Nat Neurosci, 10, 1249-1259.  
17476308 W.Feng, H.Wu, L.N.Chan, and M.Zhang (2007).
The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization.
  EMBO J, 26, 2786-2796.
PDB code: 2ns5
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
16835239 K.Matsuda, S.Matsuda, C.M.Gladding, and M.Yuzaki (2006).
Characterization of the delta2 glutamate receptor-binding protein delphilin: Splicing variants with differential palmitoylation and an additional PDZ domain.
  J Biol Chem, 281, 25577-25587.  
16858411 L.E.Swan, M.Schmidt, T.Schwarz, E.Ponimaskin, U.Prange, T.Boeckers, U.Thomas, and S.J.Sigrist (2006).
Complex interaction of Drosophila GRIP PDZ domains and Echinoid during muscle morphogenesis.
  EMBO J, 25, 3640-3651.  
16637659 M.A.Stiffler, V.P.Grantcharova, M.Sevecka, and G.MacBeath (2006).
Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays.
  J Am Chem Soc, 128, 5913-5922.  
16007100 J.F.Long, W.Feng, R.Wang, L.N.Chan, F.C.Ip, J.Xia, N.Y.Ip, and M.Zhang (2005).
Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem.
  Nat Struct Mol Biol, 12, 722-728.
PDB codes: 1u37 1u38 1u39 1u3b
16049001 S.Gianni, A.Engström, M.Larsson, N.Calosci, F.Malatesta, L.Eklund, C.C.Ngang, C.Travaglini-Allocatelli, and P.Jemth (2005).
The kinetics of PDZ domain-ligand interactions and implications for the binding mechanism.
  J Biol Chem, 280, 34805-34812.  
15698575 T.Cierpicki, J.H.Bushweller, and Z.S.Derewenda (2005).
Probing the supramodular architecture of a multidomain protein: the structure of syntenin in solution.
  Structure, 13, 319-327.  
14988405 C.Bécamel, S.Gavarini, B.Chanrion, G.Alonso, N.Galéotti, A.Dumuis, J.Bockaert, and P.Marin (2004).
The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins.
  J Biol Chem, 279, 20257-20266.  
15250762 C.Biskup, L.Kelbauskas, T.Zimmer, K.Benndorf, A.Bergmann, W.Becker, J.P.Ruppersberg, C.Stockklausner, and N.Klöcker (2004).
Interaction of PSD-95 with potassium channels visualized by fluorescence lifetime-based resonance energy transfer imaging.
  J Biomed Opt, 9, 753-759.  
15378037 E.Kim, and M.Sheng (2004).
PDZ domain proteins of synapses.
  Nat Rev Neurosci, 5, 771-781.  
15030393 T.Iwamoto, Y.Yamada, K.Hori, Y.Watanabe, K.Sobue, and M.Inui (2004).
Differential modulation of NR1-NR2A and NR1-NR2B subtypes of NMDA receptor by PDZ domain-containing proteins.
  J Neurochem, 89, 100-108.  
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
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 codes are shown on the right.