Počet záznamů: 1

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

SYSNO ASEP	0544647
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains
Tvůrce(i)	Pohl, Pavel (FGU-C)_ORCID Joshi, Rohit (FGU-C) Petrvalská, Olivia (FGU-C)_{RID, ORCID, SAI} Obšil, Tomáš (FGU-C)_{RID, ORCID} Obšilová, Veronika (FGU-C)_{RID, ORCID, SAI}
Číslo článku	899
Zdroj.dok.	Communications Biology. - : Nature Publishing Group Roč. 4, č. 1 (2021)
Poč.str.	15 s.
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	protein structure and function ; ubiquitination ; 14-3-3 protein ; Nedd4-2 ubiquitin ligase ; phosphorylation
Vědní obor RIV	CE - Biochemie
Obor OECD	Biochemistry and molecular biology
CEP	GA20-00058S GA ČR - Grantová agentura ČR
Výzkumná infrastruktura	CIISB - 90043 - Masarykova univerzita
Způsob publikování	Open access
Institucionální podpora	FGU-C - RVO:67985823
UT WOS	000680395000002
EID SCOPUS	85111089437
DOI	10.1038/s42003-021-02419-0
Anotace	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 Ser342 and Ser448 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.
Pracoviště	Fyziologický ústav
Kontakt	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Rok sběru	2022
Elektronická adresa	https://doi.org/10.1038/s42003-021-02419-0

Počet záznamů: 1