Informace o projektu
Computational chemistry for Wnt signaling pathway
- Kód projektu
- MUNI/G/1100/2016
- Období řešení
- 3/2017 - 12/2019
- Investor / Programový rámec / typ projektu
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Masarykova univerzita
- Grantová agentura MU
- INTERDISCIPLINARY - Mezioborové výzkumné projekty
- Fakulta / Pracoviště MU
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Přírodovědecká fakulta
- prof. Mgr. Vítězslav Bryja, Ph.D.
- Mgr. Jakub Harnoš, Ph.D.
- Mgr. Marek Kravec, Ph.D.
- Další fakulta/pracoviště MU
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Středoevropský technologický institut
- prof. RNDr. Robert Vácha, PhD.
- Tereza Gerguri
- Mgr. Alžběta Türková
Wnt signaling pathway is a one of the most important signaling routes required for the communication among cells, which is crucial for tissue homeostasis. Despite the clear (patho-)physiological relevance of Wnt signaling pathway, the molecular mechanisms regulating the pathway are poorly known. The proposed project will address several long standing questions related to the molecular regulation of Wnt signal transduction in the cytoplasm. We will focus on the key cytoplasmic protein regulator – Dishevelled (DVL) – which is heavily phosphorylated in response to Wnt stimuli and which, by unknown mechanisms, regulates strength and direction of downstream signaling. Specifically, we will use the combination of experimental data and computational modelling to get insight into the molecular mechanisms, which control cell membrane recruitment of human DVL, and which regulate DVL conformation. Experiments from Bryja´s group focused on identification of the post-translational modifications (mainly phosphorylations) and intermolecular interactions of DVL in various functional states will create a basis for in silico modelling. Computer simulations from Vacha’s team will complement the experiment with molecular details on stability and mechanism of individual conformations. The in silico results will then in turn guide further experiments, which will confirm/not confirm the computer predictions. We believe that the combined approach will overcome the current limits of the individual methods and together we will provide the mechanism how DVL performs its multiple functions.
Publikace
Počet publikací: 8
2021
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Phosphorylation-induced changes in the PDZ domain of Dishevelled 3
Scientific Reports, rok: 2021, ročník: 11, vydání: 1, DOI
2020
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Effect of membrane composition on DivIVA-membrane interaction.
BBA Biomembranes, rok: 2020, ročník: 1862, vydání: 8, DOI
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Magainin 2 and PGLa in Bacterial Membrane Mimics II: Membrane Fusion and Sponge Phase Formation.
Biophysical Journal, rok: 2020, ročník: 118, vydání: 3, DOI
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Yeast Spt6 Reads Multiple Phosphorylation Patterns of RNA Polymerase II C-Terminal Domain In Vitro
Journal of Molecular Biology, rok: 2020, ročník: 432, vydání: 14, DOI
2019
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Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1
Nature Communications, rok: 2019, ročník: 10, vydání: APR 18 2019, DOI
2018
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Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays
Journal of Biological Chemistry, rok: 2018, ročník: 293, vydání: 42, DOI
2017
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The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?
Critical Reviews in Biochemistry and Molecular Biology, rok: 2017, ročník: 52, vydání: 6, DOI
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The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/beta-Catenin Signaling in Mammalian Cells
Molecular and cellular biology, rok: 2017, ročník: 37, vydání: 18, DOI