Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F22%3A00556577" target="_blank" >RIV/67985823:_____/22:00556577 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/22:10445555 RIV/00216208:11320/22:10445555 RIV/00216224:14740/22:00128768 RIV/00216224:90127/22:00140003

Result on the web

<a href="https://doi.org/10.1016/j.bpj.2022.02.025" target="_blank" >https://doi.org/10.1016/j.bpj.2022.02.025</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpj.2022.02.025" target="_blank" >10.1016/j.bpj.2022.02.025</a>

Result language

angličtina

Original language name

Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains

Original language description

Neural precursor cells expressed developmentally downregulated protein 4-2 (Nedd4-2), a homologous to the E6-AP carboxyl terminus (HECT) ubiquitin ligase, triggers the endocytosis and degradation of its downstream target molecules by regulating signal transduction through interactions with other targets, including 14-3-3 proteins. In our previous study, we found that 14-3-3 binding induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains. Here, we used time-resolved fluorescence intensity and anisotropy decay measurements, together with fluorescence quenching and mass spectrometry, to further characterize interactions between Nedd4-2 and 14-3-3 proteins. The results showed that 14-3-3 binding affects the emission properties of AEDANS-labeled WW3, WW4, and, to a lesser extent, WW2 domains, and reduces their mobility, but not those of the WW1 domain, which remains mobile. In contrast, 14-3-3 binding has the opposite effect on the active site of the HECT domain, which is more solvent exposed and mobile in the complexed form than in the apo form of Nedd4-2. Overall, our results suggest that steric hindrance of the WW3 and WW4 domains combined with conformational changes in the catalytic domain may account for the 14-3-3 binding-mediated regulation of Nedd4-2.

Czech name

—

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

<a href="/en/project/GA20-00058S" target="_blank" >GA20-00058S: Phosphorylation dependent regulation of human ubiquitin ligase NEDD4-2</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

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

Name of the periodical

Biophysical Journal

ISSN

0006-3495

e-ISSN

1542-0086

Volume of the periodical

121

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

1299-1311

UT code for WoS article

000784358200017

EID of the result in the Scopus database

2-s2.0-85125674050