Crystal structure of the PDZ domain of mouse Dishevelled 1 and its interaction with CXXC5

Inhwan Lee, Sooho Choi, Ji Hye Yun, Seol hwa Seo, Sehee Choi, Kang Yell Choi, Weontae Lee

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development. Here, we determined the first crystal structure of the Dvl-1 PDZ domain at a resolution of 1.76 Å, and compared it with its previously reported solution structure. The Dvl1 PDZ domain crystal belonged to the space group H32 with unit-cell parameters a = b = 72.837, c = 120.616, α = β = 90.00, γ = 120.00. The crystal structure of Dvl1 PDZ shared its topology with the previously reported structure determined by nuclear magnetic resonance (NMR); however, the crystal structure was quite different from the solution structure in both the secondary structural region and the ligand-binding pocket. Molecular modeling based on NMR and X-ray crystallographic data yielded detailed information about the Dvl1/CXXC5 interaction, which will be useful for designing inhibitors.

Original languageEnglish
Pages (from-to)584-590
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2017 Apr 8

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) through their Mid-career Researcher Program (grant number NRF-2013R1A2A2A01068963) and the Translational Research Center for Protein Function Control (grant number 2016R1A5A1004694).

Publisher Copyright:
© 2016 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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