Structural highlights
Disease
ZO2_HUMAN Defects in TJP2 are involved in familial hypercholanemia (FHCA) [MIM:607748. FHCA is a disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption.[1]
Function
ZO2_HUMAN Plays a role in tight junctions and adherens junctions.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Domain-swapped dimerization of the second PDZ domain of ZO2 may provide a structural basis for the polymerization of claudins.,Wu J, Yang Y, Zhang J, Ji P, Du W, Jiang P, Xie D, Huang H, Wu M, Zhang G, Wu J, Shi Y J Biol Chem. 2007 Dec 7;282(49):35988-99. Epub 2007 Sep 25. PMID:17897942[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet. 2003 May;34(1):91-6. PMID:12704386 doi:10.1038/ng1147
- ↑ Wu J, Yang Y, Zhang J, Ji P, Du W, Jiang P, Xie D, Huang H, Wu M, Zhang G, Wu J, Shi Y. Domain-swapped dimerization of the second PDZ domain of ZO2 may provide a structural basis for the polymerization of claudins. J Biol Chem. 2007 Dec 7;282(49):35988-99. Epub 2007 Sep 25. PMID:17897942 doi:10.1074/jbc.M703826200
