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

J 2021

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

POHL, P., R. JOSHI, O. PETRVALSKA, T. OBSIL, V. OBSILOVA et. al.

Základní údaje

Originální název

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

Autoři

POHL, P., R. JOSHI, O. PETRVALSKA, T. OBSIL a V. OBSILOVA

Vydání

COMMUNICATIONS BIOLOGY, 2021, 2399-3642

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.548

Kód RIV

RIV/00216224:14740/21:00124534

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1038/s42003-021-02419-0

UT WoS

000680395000002

Klíčová slova anglicky

EPITHELIAL NA+ CHANNELPROTEIN-PROTEIN INTERACTIONSSTRUCTURAL BASISPROTEOMIC ANALYSISSODIUM-CHANNELSMOLECULAR-BASISPY MOTIFPHOSPHORYLATIONBINDINGSERUM

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 5. 2022 15:01, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

POHL, P., R. JOSHI, O. PETRVALSKA, T. OBSIL a V. OBSILOVA. 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains. COMMUNICATIONS BIOLOGY. 2021, roč. 4, č. 1, s. 899-913. ISSN 2399-3642. Dostupné z: https://dx.doi.org/10.1038/s42003-021-02419-0.

@article{1846844,
   author = {Pohl, P. and Joshi, R. and Petrvalska, O. and Obsil, T. and Obsilova, V.},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s42003-021-02419-0},
   keywords = {EPITHELIAL NA+ CHANNELPROTEIN-PROTEIN INTERACTIONSSTRUCTURAL BASISPROTEOMIC ANALYSISSODIUM-CHANNELSMOLECULAR-BASISPY MOTIFPHOSPHORYLATIONBINDINGSERUM},
   language = {eng},
   issn = {2399-3642},
   journal = {COMMUNICATIONS BIOLOGY},
   title = {14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains},
   url = {https://www.nature.com/articles/s42003-021-02419-0.pdf},
   volume = {4},
   year = {2021}
}

TY  - JOUR
ID  - 1846844
AU  - Pohl, P. - Joshi, R. - Petrvalska, O. - Obsil, T. - Obsilova, V.
PY  - 2021
TI  - 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains
JF  - COMMUNICATIONS BIOLOGY
VL  - 4
IS  - 1
SP  - 899
EP  - 899
SN  - 23993642
KW  - EPITHELIAL NA+ CHANNELPROTEIN-PROTEIN INTERACTIONSSTRUCTURAL BASISPROTEOMIC ANALYSISSODIUM-CHANNELSMOLECULAR-BASISPY MOTIFPHOSPHORYLATIONBINDINGSERUM
UR  - https://www.nature.com/articles/s42003-021-02419-0.pdf
N2  - 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.
ER  -

POHL, P., R. JOSHI, O. PETRVALSKA, T. OBSIL a V. OBSILOVA. 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains. \textit{COMMUNICATIONS BIOLOGY}. 2021, roč.~4, č.~1, s.~899-913. ISSN~2399-3642. Dostupné z: https://dx.doi.org/10.1038/s42003-021-02419-0.

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