Dishevelled (DVL) is a key component of the Wnt signalling pathway, which governs a wide range of biological processes (cell proliferation, migration and differentiation, stem cell renewal, cell polarity). It is involved in both canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) cell signalling pathways [1]. Dishevelled protein was first discovered in Drosophila mutants with disordered hair and bristle polarity [2], and it was proved that it plays an important role in embryogenesis. Dishevelled proteins are also connected with the process of cancerogenesis in humans, and mutations/dysregulation of Wnt pathway components are associated with certain carcinomas [3].
Dishevelled proteins consist of three conserved domains: N-terminal DIX domain, central PDZ domain, and C-terminal DEP domain, that are linked by an unstructured basic region (DIX-PDZ) and proline-rich region (PDZ-DEP) [4]. As a scaffolding protein, DVL uses its domains for interaction with a wide range of human proteins [1]. Its activity is affected by post-translational modifications (phosphorylation, ubiquitination and acetylation) [3, 5], however, the exact way how Dishevelled proteins integrate and relay the complex signals to perform such a broad spectrum of biological activities remains unknown.
This work is focused on the crystallization and structure determination of the PDZ domain of human Dishevelled-3 (DVL3) protein. A 1.4 Å diffraction data were collected and the structure of PDZ was solved by the molecular replacement method.
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5. M. Sharma, D. Molehin, I. Castro-Piedras, E. G. Martinez, K. Pruitt. Sci Rep 9(1) (2019) 16257
We acknowledge CMS-Biocev ("Biophysical techniques, Crystallization, Diffraction, Structural mass spectrometry”) supported by MEYS CR (LM2018127).