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Article

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.
Molecules 2018, 23(10), 2465; https://doi.org/10.3390/molecules23102465
Received: 9 July 2018 / Revised: 20 September 2018 / Accepted: 23 September 2018 / Published: 26 September 2018
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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MDPI and ACS Style

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. https://doi.org/10.3390/molecules23102465

AMA Style

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(10):2465. https://doi.org/10.3390/molecules23102465

Chicago/Turabian Style

Hiroaki, Hidekazu; Satomura, Kaori; Goda, Natsuko; Nakakura, Yukako; Hiranuma, Minami; Tenno, Takeshi; Hamada, Daizo; Ikegami, Takahisa. 2018. "Spatial Overlap of Claudin- and Phosphatidylinositol Phosphate-Binding Sites on the First PDZ Domain of Zonula Occludens 1 Studied by NMR" Molecules 23, no. 10: 2465. https://doi.org/10.3390/molecules23102465

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