PDBsum entry 2h2c

Cell adhesion

PDB id: 2h2c

Contents

Protein chain

107 a.a. *

Waters ×43

* Residue conservation analysis

PDB id:

2h2c

Name:

Cell adhesion

Title:

Crystal structure of zo-1 pdz1 bound to a phage-derived ligand (wrrttwv)

Structure:

Tight junction protein zo-1. Chain: a. Fragment: first pdz domain. Synonym: zonula occludens 1 protein, zona occludens 1 protein, tight junction protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: zo1 (tjp1). Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.00Å R-factor: 0.210 R-free: 0.225

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

Date:

18-May-06 Release date: 13-Jun-06

Protein chain

Q07157  (ZO1_HUMAN) -  Tight junction protein ZO-1 from Homo sapiens

Seq: 1748 a.a.

Struc: 107 a.a.*

* PDB and UniProt seqs differ at 14 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.

ABSTRACT

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.