PDBsum entry 1n99

Go to PDB code: 
protein Protein-protein interface(s) links
Signaling protein PDB id
Protein chain
162 a.a. *
Waters ×254
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the pdz tandem of human syntenin
Structure: Syntenin 1. Chain: a, b. Fragment: pdz tandem. Synonym: syndecan binding protein 1, melanoma differentiati associated protein-9, mda-9, scaffold protein pbp1, pro-tgf cytoplasmic domain-interacting protein 18, tacip18. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sdcbp or mda9 or sycl. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
1.94Å     R-factor:   0.186     R-free:   0.227
Authors: B.S.Kang,D.R.Cooper,F.Jelen,Y.Devedjiev,U.Derewenda,Z.Dauter J.Otlewski,Z.S.Derewenda
Key ref:
B.S.Kang et al. (2003). PDZ tandem of human syntenin: crystal structure and functional properties. Structure, 11, 459-468. PubMed id: 12679023 DOI: 10.1016/S0969-2126(03)00052-2
22-Nov-02     Release date:   15-Apr-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O00560  (SDCB1_HUMAN) -  Syntenin-1
298 a.a.
162 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   3 terms 


DOI no: 10.1016/S0969-2126(03)00052-2 Structure 11:459-468 (2003)
PubMed id: 12679023  
PDZ tandem of human syntenin: crystal structure and functional properties.
B.S.Kang, D.R.Cooper, F.Jelen, Y.Devedjiev, U.Derewenda, Z.Dauter, J.Otlewski, Z.S.Derewenda.
Syntenin, a 33 kDa protein, interacts with several cell membrane receptors and with merlin, the product of the causal gene for neurofibromatosis type II. We report a crystal structure of the functional fragment of human syntenin containing two canonical PDZ domains, as well as binding studies for full-length syntenin, the PDZ tandem, and isolated PDZ domains. We show that the functional properties of syntenin are a result of independent interactions with target peptides, and that each domain is able to bind peptides belonging to two different classes: PDZ1 binds peptides from classes I and III, while PDZ2 interacts with classes I and II. The independent binding of merlin by PDZ1 and syndecan-4 by PDZ2 provides direct evidence for the coupling of syndecan-mediated signaling to actin regulation by merlin.
  Selected figure(s)  
Figure 2.
Figure 2. A Comparison of PDZ1 and PDZ2 Domains of Syntenin(A) Superposition of the two PDZ domains of syntenin. PDZ1 is gold and PDZ2 is blue. The a2 helices have been superposed to show the similarity of the fold, yet emphasize the differences of the peptide binding groove. The same orientation is used for all three figures.(B) The peptide binding surface of PDZ1. The electrostatic potential surface is shown with select residues that surround the peptide binding groove labeled. A superposed C-terminal CRIPT-derived peptide from the structure of PSD-95 (1BE9 [23]) is shown semitransparent, with side chains represented as cyan spheres in the b carbon position. The approximate locations of the P[0], P[-1], and P[-2] binding pockets are indicated by gold, pink, and green circles, respectively.(C) The peptide binding surface of PDZ2 represented as described in (B). Figures were made using MOLSCRIPT [47] (A) and POVSCRIPT+ ( (B and C) and rendered with RASTER3D [48]. Electrostatic potentials were calculated in GRASP [49].
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 459-468) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20461427 K.Kaufmann, N.Shen, L.Mizoue, and J.Meiler (2011).
A physical model for PDZ-domain/peptide interactions.
  J Mol Model, 17, 315-324.  
20228839 H.Boukerche, H.Aissaoui, C.Prévost, H.Hirbec, S.K.Das, Z.Z.Su, D.Sarkar, and P.B.Fisher (2010).
Src kinase activation is mandatory for MDA-9/syntenin-mediated activation of nuclear factor-kappaB.
  Oncogene, 29, 3054-3066.  
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
20565253 J.R.Couchman (2010).
Transmembrane signaling proteoglycans.
  Annu Rev Cell Dev Biol, 26, 89.  
20142502 J.Yan, L.Pan, X.Chen, L.Wu, and M.Zhang (2010).
The structure of the harmonin/sans complex reveals an unexpected interaction mode of the two Usher syndrome proteins.
  Proc Natl Acad Sci U S A, 107, 4040-4045.
PDB code: 3k1r
19228696 B.Sulka, H.Lortat-Jacob, R.Terreux, F.Letourneur, and P.Rousselle (2009).
Tyrosine dephosphorylation of the syndecan-1 PDZ binding domain regulates syntenin-1 recruitment.
  J Biol Chem, 284, 10659-10671.  
  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.  
17474715 D.Saro, T.Li, C.Rupasinghe, A.Paredes, N.Caspers, and M.R.Spaller (2007).
A thermodynamic ligand binding study of the third PDZ domain (PDZ3) from the mammalian neuronal protein PSD-95.
  Biochemistry, 46, 6340-6352.  
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
17473018 Q.Chen, X.Niu, Y.Xu, J.Wu, and Y.Shi (2007).
Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex.
  Protein Sci, 16, 1053-1062.
PDB code: 2ain
17187376 R.Enz (2007).
The trick of the tail: protein-protein interactions of metabotropic glutamate receptors.
  Bioessays, 29, 60-73.  
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.  
16908530 N.Latysheva, G.Muratov, S.Rajesh, M.Padgett, N.A.Hotchin, M.Overduin, and F.Berditchevski (2006).
Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63.
  Mol Cell Biol, 26, 7707-7718.  
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
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.  
14725761 T.Walma, J.Aelen, S.B.Nabuurs, M.Oostendorp, L.van den Berk, W.Hendriks, and G.W.Vuister (2004).
A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second PDZ domain of PTP-BL.
  Structure, 12, 11-20.
PDB code: 1ozi
12842047 B.S.Kang, D.R.Cooper, Y.Devedjiev, U.Derewenda, and Z.S.Derewenda (2003).
Molecular roots of degenerate specificity in syntenin's PDZ2 domain: reassessment of the PDZ recognition paradigm.
  Structure, 11, 845-853.
PDB codes: 1nte 1obx 1oby 1obz
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 code is shown on the right.