Molecular mechanism of E3 ubiquitin ligase Nedd4-2 regulation
Public support
Provider
Czech Science Foundation
Programme
Standard projects
Call for proposals
SGA0202600001
Main participants
Fyziologický ústav AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
26-20379S
Alternative language
Project name in Czech
Molecular mechanism of E3 ubiquitin ligase Nedd4-2 regulation
Annotation in Czech
The main goal of this project is to elucidate the molecular mechanisms governing the regulation of Nedd4-2, a key E3 ubiquitin ligase that regulates ion channels and membrane receptors, impacting diseases such as epilepsy and hypertension. Despite its critical role, the regulatory mechanisms of Nedd4-2, in particular the role of its binding partners, remain poorly understood, limiting therapeutic advances. To address this knowledge gap, we will use cryo-electron microscopy, biochemical, and biophysical techniques to determine the structure of the Nedd4-2:14-3-3 complex and characterize interactions between Nedd4-2 and NDFIP1/2 and calmodulin. Building on our recent findings, in particular the cryo-EM structure of full-length Nedd4-2, we will investigate how these binding partners influence the structure and catalytic activity of Nedd4-2. By providing detailed insights into these interactions, our study will advance the understanding of Nedd4-2 regulation and pave the way for the development of novel therapeutic strategies targeting diseases associated with its dysfunction.
Scientific branches
R&D category
ZV - Basic research
OECD FORD - main branch
20301 - Mechanical engineering
OECD FORD - secondary branch
10608 - Biochemistry and molecular biology
OECD FORD - another secondary branch
10609 - Biochemical research methods
CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)
CE - Biochemistry<br>EB - Genetics and molecular biology<br>JR - Other machinery industry<br>JT - Propulsion, engines and fuels
Solution timeline
Realization period - beginning
Jan 1, 2026
Realization period - end
Dec 31, 2028
Project status
Z - Beginning multi-year project
Latest support payment
—
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP26-GA0-GA-R
Data delivery date
May 19, 2026
Finance
Total approved costs
13,783 thou. CZK
Public financial support
13,412 thou. CZK
Other public sources
371 thou. CZK
Non public and foreign sources
0 thou. CZK