PDBsum entry 1q3o

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protein metals Protein-protein interface(s) links
Peptide binding protein PDB id
Protein chains
104 a.a. *
104 a.a. *
_BR ×5
Waters ×94
* Residue conservation analysis
PDB id:
Name: Peptide binding protein
Title: Crystal structure of the shank pdz-ligand complex reveals a class i pdz interaction and a novel pdz-pdz dimerization
Structure: Shank1. Chain: a, b. Fragment: pdz domain. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: shank1a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.80Å     R-factor:   0.234     R-free:   0.251
Authors: Y.J.Im,J.H.Lee,S.H.Park,S.J.Park,S.-H.Rho,G.B.Kang,E.Kim, S.H.Eom
Key ref:
Y.J.Im et al. (2003). Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization. J Biol Chem, 278, 48099-48104. PubMed id: 12954649 DOI: 10.1074/jbc.M306919200
31-Jul-03     Release date:   27-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9WV48  (SHAN1_RAT) -  SH3 and multiple ankyrin repeat domains protein 1
2167 a.a.
104 a.a.
Protein chain
Pfam   ArchSchema ?
Q9WV48  (SHAN1_RAT) -  SH3 and multiple ankyrin repeat domains protein 1
2167 a.a.
104 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain


DOI no: 10.1074/jbc.M306919200 J Biol Chem 278:48099-48104 (2003)
PubMed id: 12954649  
Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization.
Y.J.Im, J.H.Lee, S.H.Park, S.J.Park, S.H.Rho, G.B.Kang, E.Kim, S.H.Eom.
The Shank/proline-rich synapse-associated protein family of multidomain proteins is known to play an important role in the organization of synaptic multiprotein complexes. For instance, the Shank PDZ domain binds to the C termini of guanylate kinase-associated proteins, which in turn interact with the guanylate kinase domain of postsynaptic density-95 scaffolding proteins. Here we describe the crystal structures of Shank1 PDZ in its peptide free form and in complex with the C-terminal hexapeptide (EAQTRL) of guanylate kinase-associated protein (GKAP1a) determined at 1.8- and 2.25-A resolutions, respectively. The structure shows the typical class I PDZ interaction of PDZ-peptide complex with the consensus sequence -X-(Thr/Ser)-X-Leu. In addition, Asp-634 within the Shank1 PDZ domain recognizes the positively charged Arg at -1 position and hydrogen bonds, and salt bridges between Arg-607 and the side chains of the ligand at -3 and -5 positions contribute further to the recognition of the peptide ligand. Remarkably, whether free or complexed, Shank1 PDZ domains form dimers with a conserved beta B/beta C loop and N-terminal beta A strands, suggesting a novel model of PDZ-PDZ homodimerization. This implies that antiparallel dimerization through the N-terminal beta A strands could be a common configuration among PDZ dimers. Within the dimeric structure, the two-peptide binding sites are arranged so that the N termini of the bound peptide ligands are in close proximity and oriented toward the 2-fold axis of the dimer. This configuration may provide a means of facilitating dimeric organization of PDZ-target assemblies.
  Selected figure(s)  
Figure 1.
FIG. 1. Structure of the SHANK1 PDZ domain. A, stereoview of a ribbon diagram showing the monomeric structure of the Shank PDZ-ligand complex. The -strands are labeled A- F, and the -helices are labeled A and B. The ligand is colored dark gray. The dotted line indicates a disordered loop (residues 610-614) that is not seen in peptide-bound structure. All of the residues in the loop were observed in peptide-free structure. B, amino acid sequence alignment of the PDZ domains from the rat and human Shank family, human NHERF (37), rat PSD95 (26), and rat GRIP1 (35). The sequences were aligned using the program ClustalX (38). Highly conserved residues are shaded in black and gray. The secondary structure elements of Shank1 PDZ are shown as arrows ( -strands), bars ( -helices), and lines (connecting loops). C, superposition of the PDZ domains. Black ribbon indicates Shank1 PDZ domain. Light and dark gray ribbons indicate PDZ domains of human NHERF (Protein Data Bank code 1G9O [PDB] ) and rat PSD95 (Protein Data Bank code 1BFE [PDB] ), respectively.
Figure 3.
FIG. 3. Overall structures of the PDZ dimer. A, Shank1 PDZ dimer. The black arrow indicates the N-terminal end of each peptide ligand. B, ribbon diagram of the GRIP PDZ6 dimer (Protein Data Bank code 1N7F [PDB] ). C, Shank PDZ dimer interface. Side chains of hydrophobic residues at the interface are shown as ball and stick models. D, amino acid sequence and predicted secondary structure of the C-terminal domain of PIX. The secondary structure was predicted using the PredictProtein Web server ( E, proposed model of the Shank1 PDZ and PIX C terminus complex. The figures were made using PyMOL (
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 48099-48104) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21376703 J.H.Lee, H.Park, S.J.Park, H.J.Kim, and S.H.Eom (2011).
The structural flexibility of the shank1 PDZ domain is important for its binding to different ligands.
  Biochem Biophys Res Commun, 407, 207-212.
PDB codes: 3qjm 3qjn
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
20026484 O.Sakarya, C.Conaco, O.Egecioglu, S.A.Solla, T.H.Oakley, and K.S.Kosik (2010).
Evolutionary expansion and specialization of the PDZ domains.
  Mol Biol Evol, 27, 1058-1069.  
20715264 W.S.Iskenderian-Epps, and B.Imperiali (2010).
Modulation of Shank3 PDZ domain ligand-binding affinity by dimerization.
  Chembiochem, 11, 1979-1984.  
19581411 D.Sengupta, S.Truschel, C.Bachert, and A.D.Linstedt (2009).
Organelle tethering by a homotypic PDZ interaction underlies formation of the Golgi membrane network.
  J Cell Biol, 186, 41-55.  
  19342771 H.Chen, S.Tong, X.Li, J.Wu, Z.Zhu, L.Niu, and M.Teng (2009).
Structure of the second PDZ domain from human zonula occludens 2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 327-330.
PDB code: 3e17
19345194 M.K.Hayashi, C.Tang, C.Verpelli, R.Narayanan, M.H.Stearns, R.M.Xu, H.Li, C.Sala, and Y.Hayashi (2009).
The postsynaptic density proteins Homer and Shank form a polymeric network structure.
  Cell, 137, 159-171.
PDB codes: 3cve 3cvf
18618698 Y.Kong, and M.Karplus (2009).
Signaling pathways of PDZ2 domain: a molecular dynamics interaction correlation analysis.
  Proteins, 74, 145-154.  
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.  
17928286 A.S.Fanning, M.F.Lye, J.M.Anderson, and A.Lavie (2007).
Domain swapping within PDZ2 is responsible for dimerization of ZO proteins.
  J Biol Chem, 282, 37710-37716.
PDB code: 2rcz
17121805 K.Handa, T.Yugawa, M.Narisawa-Saito, S.Ohno, M.Fujita, and T.Kiyono (2007).
E6AP-dependent degradation of DLG4/PSD95 by high-risk human papillomavirus type 18 E6 protein.
  J Virol, 81, 1379-1389.  
17279591 M.Paduch, M.Biernat, P.Stefanowicz, Z.S.Derewenda, Z.Szewczuk, and J.Otlewski (2007).
Bivalent peptides as models for multimeric targets of PDZ domains.
  Chembiochem, 8, 443-452.  
17962403 S.T.Runyon, Y.Zhang, B.A.Appleton, S.L.Sazinsky, P.Wu, B.Pan, C.Wiesmann, N.J.Skelton, and S.S.Sidhu (2007).
Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3.
  Protein Sci, 16, 2454-2471.
PDB codes: 2joa 2p3w
17396155 T.Sugi, T.Oyama, T.Muto, S.Nakanishi, K.Morikawa, and H.Jingami (2007).
Crystal structures of autoinhibitory PDZ domain of Tamalin: implications for metabotropic glutamate receptor trafficking regulation.
  EMBO J, 26, 2192-2205.
PDB codes: 2egk 2egn 2ego
17656586 Y.Zhang, B.A.Appleton, P.Wu, C.Wiesmann, and S.S.Sidhu (2007).
Structural and functional analysis of the ligand specificity of the HtrA2/Omi PDZ domain.
  Protein Sci, 16, 1738-1750.
PDB code: 2pzd
17267502 Y.Zhang, J.Dasgupta, R.Z.Ma, L.Banks, M.Thomas, and X.S.Chen (2007).
Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein.
  J Virol, 81, 3618-3626.
PDB codes: 2i04 2i0i 2i0l
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.  
17002371 N.Basdevant, H.Weinstein, and M.Ceruso (2006).
Thermodynamic basis for promiscuity and selectivity in protein-protein interactions: PDZ domains, a case study.
  J Am Chem Soc, 128, 12766-12777.  
16962991 R.H.Kedlaya, K.M.Bhat, J.Mitchell, S.J.Darnell, and V.Setaluri (2006).
TRP1 interacting PDZ-domain protein GIPC forms oligomers and is localized to intracellular vesicles in human melanocytes.
  Arch Biochem Biophys, 454, 160-169.  
16132821 A.E.Duquesne, M.Ruijter, J.Brouwer, J.W.Drijfhout, S.B.Nabuurs, C.A.Spronk, G.W.Vuister, M.Ubbink, and G.W.Canters (2005).
Solution structure of the second PDZ domain of the neuronal adaptor X11alpha and its interaction with the C-terminal peptide of the human copper chaperone for superoxide dismutase.
  J Biomol NMR, 32, 209-218.
PDB code: 1y7n
16283141 E.Kalay, Brouwer, R.Caylan, S.B.Nabuurs, B.Wollnik, A.Karaguzel, J.G.Heister, H.Erdol, F.P.Cremers, C.W.Cremers, H.G.Brunner, and H.Kremer (2005).
A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.
  J Mol Med, 83, 1025-1032.  
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.  
15231733 C.L.Kielkopf, S.Lücke, and M.R.Green (2004).
U2AF homology motifs: protein recognition in the RRM world.
  Genes Dev, 18, 1513-1526.  
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.  
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.