14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90043%2F21%3A00140001" target="_blank" >RIV/00216224:90043/21:00140001 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/21:00544647 RIV/00216208:11310/21:10429569 RIV/00216208:11130/21:10429569

Result on the web

<a href="https://www.nature.com/articles/s42003-021-02419-0.pdf" target="_blank" >https://www.nature.com/articles/s42003-021-02419-0.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s42003-021-02419-0" target="_blank" >10.1038/s42003-021-02419-0</a>

Result language

angličtina

Original language name

14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains

Original language description

Neural precursor cell expressed developmentally down-regulated 4 ligase (Nedd4-2) is an E3 ubiquitin ligase that targets proteins for ubiquitination and endocytosis, thereby regulating numerous ion channels, membrane receptors and tumor suppressors. Nedd4-2 activity is regulated by autoinhibition, calcium binding, oxidative stress, substrate binding, phosphorylation and 14-3-3 protein binding. However, the structural basis of 14-3-3-mediated Nedd4-2 regulation remains poorly understood. Here, we combined several techniques of integrative structural biology to characterize Nedd4-2 and its complex with 14-3-3. We demonstrate that phosphorylated Ser(342) and Ser(448) are the key residues that facilitate 14-3-3 protein binding to Nedd4-2 and that 14-3-3 protein binding induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains. Overall, our findings provide the structural glimpse into the 14-3-3-mediated Nedd4-2 regulation and highlight the potential of the Nedd4-2:14-3-3 complex as a pharmacological target for Nedd4-2-associated diseases such as hypertension, epilepsy, kidney disease and cancer. Pohl et al. investigated the structural basis of Nedd4-2 regulation by 14-3-3 and found that phosphorylated Ser342 and Ser448 are the main residues that facilitate 14-3-3 binding to Nedd4-2. The authors propose that the Nedd4-2:14-3-3 complex then stimulates a structural rearrangement of Nedd4-2 through inhibiting interaction of its structured domains.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

—

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

COMMUNICATIONS BIOLOGY

ISSN

2399-3642

e-ISSN

2399-3642

Volume of the periodical

4

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

15

Pages from-to

899

UT code for WoS article

000680395000002

EID of the result in the Scopus database

2-s2.0-85111089437