PDBsum entry 2osg

Cell adhesion

PDB id: 2osg

Contents

Protein chain

83 a.a. *

* Residue conservation analysis

PDB id:

2osg

Name:

Cell adhesion

Title:

Solution structure and binding property of the domain-swapped dimer of zo2pdz2

Structure:

Tight junction protein zo-2. Chain: a, b. Fragment: zo2pdz2 domain. Synonym: tight junction associated protein, zonula occludens 2 protein, zona occludens 2 protein, tight junction protein 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: brain. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

J.W.Wu,Y.S.Yang,J.H.Zhang,P.Ji,J.H.Wu,Y.Y.Shi

Key ref:

J.Wu et al. (2007). Domain-swapped dimerization of the second PDZ domain of ZO2 may provide a structural basis for the polymerization of claudins. J Biol Chem, 282, 35988-35999. PubMed id: 17897942 DOI: 10.1074/jbc.M703826200

Date:

05-Feb-07 Release date: 25-Sep-07

Protein chains

Q9UDY2  (ZO2_HUMAN) -  Tight junction protein ZO-2 from Homo sapiens

Seq: 1190 a.a.

Struc: 83 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M703826200

J Biol Chem 282:35988-35999 (2007)

PubMed id: 17897942

Domain-swapped dimerization of the second PDZ domain of ZO2 may provide a structural basis for the polymerization of claudins.

J.Wu, Y.Yang, J.Zhang, P.Ji, W.Du, P.Jiang, D.Xie, H.Huang, M.Wu, G.Zhang, J.Wu, Y.Shi.

ABSTRACT

Zonula occludens proteins (ZOs), including ZO1/2/3, are tight junction-associated proteins. Each of them contains three PDZ domains. It has been demonstrated that ZO1 can form either homodimers or heterodimers with ZO2 or ZO3 through the second PDZ domain. However, the underlying structural basis is not well understood. In this study, the solution structure of the second PDZ domain of ZO2 (ZO2-PDZ2) was determined using NMR spectroscopy. The results revealed a novel dimerization mode for PDZ domains via three-dimensional domain swapping, which can be generalized to homodimers of ZO1-PDZ2 or ZO3-PDZ2 and heterodimers of ZO1-PDZ2/ZO2-PDZ2 or ZO1-PDZ2/ZO3-PDZ2 due to high conservation between PDZ2 domains in ZO proteins. Furthermore, GST pulldown experiments and immunoprecipitation studies demonstrated that interactions between ZO1-PDZ2 and ZO2-PDZ2 and their self-associations indeed exist both in vitro and in vivo. Chemical cross-linking and dynamic laser light scattering experiments revealed that both ZO1-PDZ2 and ZO2-PDZ2 can form oligomers in solution. This PDZ domain-mediated oligomerization of ZOs may provide a structural basis for the polymerization of claudins, namely the formation of tight junctions.

Selected figure(s)

Figure 5.
FIGURE 5. Structure of ZO2-PDZ2. A, backbone overlay of 20 NMR structures with the lowest energy from the final CNS v1.1 calculation. This figure was produced with MOLMOL. B, a ribbon representation of the energy-minimized average structure with the secondary structure elements labeled. This figure was produced with PyMOL (W. L. DeLano (2002) PyMOL, DeLano Scientific, San Carlos, CA); for clarity, the two chains A and B are colored in green and cyan, with their N and C termini labeled with N[A], C[A], N[B], and C[B], respectively. C, comparison of the three-dimensional structure of the GRIP2PDZ3 monomer (PDB entry: 1V62) to that of one subunit in the ZO2-PDZ2 homodimer. The backbones of some secondary structured regions of the GRIP2PDZ3 monomer (yellow, 1, 2, β3, β4, β5, and β6) and a subunit of the ZO2-PDZ2 homodimer (green, 1, 2, β2b, β3, β4, and β5) are superimposed to each other. This figure was produced with PyMOL. D, sequence alignment of the second PDZ domains of ZO proteins, GRIP2PDZ3, GRIP1PDZ6, and Shank1PDZ. The sequences were aligned using the program ESPript (Easy Sequencing in PostScript) (42). Residues identical in all sequences are colored white in the red column; conserved residues are colored red, whereas the others are in black. Secondary structure elements for ZO2-PDZ2 and Shank1PDZ are shown above or below the sequences, respectively, with helices as squiggles, strands as arrows, and turns as TT.

Figure 8.
FIGURE 8. Electrostatic surface potential representation of the ZO2-PDZ2 dimer. The molecular surfaces are colored from dark blue (most positive) to deep red (most negative) according to the local electrostatic potential on a relative scale. The orientation of the molecule in panel B is rotated 180° from panel A. The charge topology was calculated and displayed using MOLMOL.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 35988-35999) copyright 2007.

Figures were selected by an automated process.