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Molecules 2018, 23(10), 2465; https://doi.org/10.3390/molecules23102465

Spatial Overlap of Claudin- and Phosphatidylinositol Phosphate-Binding Sites on the First PDZ Domain of Zonula Occludens 1 Studied by NMR

1
Laboratory of Structural Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
2
Division of Structural Biology, Graduate School of Medicine, Kobe University, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
3
The Structural Biology Research Center and Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
4
Graduate School of Engineering and Center for Applied Structural Science (CASS), Kobe University, Minatojima Minami Machi, Chuo-ku, Kobe 650-0047, Japan
5
Institute of Protein Research, Osaka University, Suita, Osaka 565-0871, Japan
6
Structural Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama-city University, Tsurumi-ku, Yokohama 230-0045 Japan
*
Author to whom correspondence should be addressed.
Received: 9 July 2018 / Revised: 20 September 2018 / Accepted: 23 September 2018 / Published: 26 September 2018
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Abstract

Background: The tight junction is an intercellular adhesion complex composed of claudins (CLDs), occludin, and the scaffolding proteins zonula occludens 1 (ZO-1) and its two paralogs ZO-2 and ZO-3. ZO-1 is a multifunctional protein that contains three PSD95/Discs large/ZO-1(PDZ) domains. A key functional domain of ZO-1 is the first PDZ domain (ZO-1(PDZ1)) that recognizes the conserved C-termini of CLDs. Methods: In this study, we confirmed that phosphoinositides bound directly to ZO-1(PDZ1) by biochemical and solution NMR experiments. We further determined the solution structure of mouse ZO-1(PDZ1) by NMR and mapped the phosphoinositide binding site onto its molecular surface. Results: The phosphoinositide binding site was spatially overlapped with the CLD-binding site of ZO-1(PDZ1). Accordingly, inositol-hexaphosphate (phytic acid), an analog of the phosphoinositide head group, competed with ZO-1(PDZ)-CLD interaction. Conclusions: The results suggested that the PDZ domain–phosphoinositide interaction plays a regulatory role in biogenesis and homeostasis of the tight junction. View Full-Text
Keywords: phosphoinositide; protein-phospholipid interaction; PDZ domain; tight junction; NMR; chemical shift perturbation phosphoinositide; protein-phospholipid interaction; PDZ domain; tight junction; NMR; chemical shift perturbation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hiroaki, H.; Satomura, K.; Goda, N.; Nakakura, Y.; Hiranuma, M.; Tenno, T.; Hamada, D.; Ikegami, T. Spatial Overlap of Claudin- and Phosphatidylinositol Phosphate-Binding Sites on the First PDZ Domain of Zonula Occludens 1 Studied by NMR. Molecules 2018, 23, 2465.

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