PDBsum entry 2h3l

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protein Protein-protein interface(s) links
Cell adhesion PDB id
Protein chains
103 a.a. *
98 a.a. *
Waters ×268
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: Crystal structure of erbin pdz
Structure: Lap2 protein. Chain: a, b. Fragment: pdz domain. Synonym: erbb2-interacting protein, erbin, densin-180-like protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: erbin. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.00Å     R-factor:   0.148     R-free:   0.169
Authors: B.A.Appleton,Y.Zhang,P.Wu,J.P.Yin,W.Hunziker,N.J.Skelton, S.S.Sidhu,C.Wiesmann
Key ref:
B.A.Appleton et al. (2006). Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity. J Biol Chem, 281, 22312-22320. PubMed id: 16737969 DOI: 10.1074/jbc.M602901200
22-May-06     Release date:   13-Jun-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q96RT1  (LAP2_HUMAN) -  Protein LAP2
1412 a.a.
103 a.a.*
Protein chain
Pfam   ArchSchema ?
Q96RT1  (LAP2_HUMAN) -  Protein LAP2
1412 a.a.
98 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)


DOI no: 10.1074/jbc.M602901200 J Biol Chem 281:22312-22320 (2006)
PubMed id: 16737969  
Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity.
B.A.Appleton, Y.Zhang, P.Wu, J.P.Yin, W.Hunziker, N.J.Skelton, S.S.Sidhu, C.Wiesmann.
We report a structural comparison of the first PDZ domain of ZO-1 (ZO1-PDZ1) and the PDZ domain of Erbin (Erbin-PDZ). Although the binding profile of Erbin-PDZ is extremely specific ([D/E][T/S]WV(COOH)), that of ZO1-PDZ1 is similar ([R/K/S/T][T/S][W/Y][V/I/L](COOH)) but broadened by increased promiscuity for three of the last four ligand residues. Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions. Structural analyses reveal that the differences in specificity can be accounted for by two key differences in primary sequence. A reduction in the size of the hydrophobic residue at the base of the site(0) pocket enables ZO1-PDZ1 to accommodate larger C-terminal residues. A single additional difference alters the specificity of both site(-1) and site(-3). In ZO1-PDZ1, an Asp residue makes favorable interactions with both Tyr(-1) and Lys/Arg(-3). In contrast, Erbin-PDZ contains an Arg at the equivalent position, and this side chain cannot accommodate either Tyr(-1) or Lys/Arg(-3) but, instead, interacts favorably with Glu/Asp(-3). We propose a model for ligand recognition that accounts for interactions extending across the entire binding site but that highlights several key specificity switches within the PDZ domain fold.
  Selected figure(s)  
Figure 2.
FIGURE 2. Overall structure of ZO1-PDZ1. A, crystallographic dimer of ZO1-PDZ1-YL with the PDZ domains colored red and magenta and the heptapeptide ligands colored green. Regions in gray represent the tri-glycine linker between the PDZ domain and the ligand and a tetrapeptide that was fused to the N terminus as a result of the cloning procedures. B, stereoscopic representation of ZO1-PDZ1-YL with secondary structure elements labeled (PDZ domain, gray; heptapeptide, green). Structural figures were produced with PyMOL (DeLano Scientific, San Carlos, CA).
Figure 5.
FIGURE 5. Determinants of PDZ domain specificity. The structure of ZO1-PDZ1-YL is shown schematically and colored to highlight the functional elements involved in ligand recognition. The peptide ligand is colored green (core motif) and yellow (auxiliary motif). The PDZ domain functional elements are colored magenta (primary), red (secondary), and blue (tertiary). The spheres indicate key side chains of the PDZ domain that contribute to recognition of side chains within the core ligand motif.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 22312-22320) copyright 2006.  
  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
20733053 B.E.Lauffer, C.Melero, P.Temkin, C.Lei, W.Hong, T.Kortemme, and M.von Zastrow (2010).
SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane.
  J Cell Biol, 190, 565-574.  
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
20868367 T.Oka, E.Remue, K.Meerschaert, B.Vanloo, C.Boucherie, D.Gfeller, G.D.Bader, S.S.Sidhu, J.Vandekerckhove, J.Gettemans, and M.Sudol (2010).
Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling.
  Biochem J, 432, 461-472.  
20016085 A.Swistowski, Q.Zhang, M.E.Orcholski, D.Crippen, C.Vitelli, A.Kurakin, and D.E.Bredesen (2009).
Novel mediators of amyloid precursor protein signaling.
  J Neurosci, 29, 15703-15712.  
19157887 H.J.Lee, N.X.Wang, Y.Shao, and J.J.Zheng (2009).
Identification of tripeptides recognized by the PDZ domain of Dishevelled.
  Bioorg Med Chem, 17, 1701-1708.  
19477632 S.Koide (2009).
Engineering of recombinant crystallization chaperones.
  Curr Opin Struct Biol, 19, 449-457.  
19569188 T.Beuming, R.Farid, and W.Sherman (2009).
High-energy water sites determine peptide binding affinity and specificity of PDZ domains.
  Protein Sci, 18, 1609-1619.  
19252499 Y.Zhang, B.A.Appleton, C.Wiesmann, T.Lau, M.Costa, R.N.Hannoush, and S.S.Sidhu (2009).
Inhibition of Wnt signaling by Dishevelled PDZ peptides.
  Nat Chem Biol, 5, 217-219.
PDB codes: 3cbx 3cby 3cbz 3cc0
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.  
18547585 C.A.Smith, and T.Kortemme (2008).
Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction.
  J Mol Biol, 380, 742-756.  
18828675 R.Tonikian, Y.Zhang, S.L.Sazinsky, B.Currell, J.H.Yeh, B.Reva, H.A.Held, B.A.Appleton, M.Evangelista, Y.Wu, X.Xin, A.C.Chan, S.Seshagiri, L.A.Lasky, C.Sander, C.Boone, G.D.Bader, and S.S.Sidhu (2008).
A specificity map for the PDZ domain family.
  PLoS Biol, 6, e239.  
17895993 A.Kurakin, A.Swistowski, S.C.Wu, and D.E.Bredesen (2007).
The PDZ domain as a complex adaptive system.
  PLoS ONE, 2, e953.  
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
17384233 J.M.Elkins, E.Papagrigoriou, G.Berridge, X.Yang, C.Phillips, C.Gileadi, P.Savitsky, and D.A.Doyle (2007).
Structure of PICK1 and other PDZ domains obtained with the help of self-binding C-terminal extensions.
  Protein Sci, 16, 683-694.
PDB codes: 2byg 2fcf 2fne 2gzv 2he2 2he4 2i1n 2iwn 2iwp 2iwq
18079720 M.Sainlos, and B.Imperiali (2007).
Tools for investigating peptide-protein interactions: peptide incorporation of environment-sensitive fluorophores via on-resin derivatization.
  Nat Protoc, 2, 3201-3209.  
17545975 R.Tonikian, Y.Zhang, C.Boone, and S.S.Sidhu (2007).
Identifying specificity profiles for peptide recognition modules from phage-displayed peptide libraries.
  Nat Protoc, 2, 1368-1386.  
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
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
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
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.