Počet záznamů: 1
Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains
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SYSNO ASEP 0556577 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains Tvůrce(i) Joshi, Rohit (FGU-C)
Pohl, Pavel (FGU-C) ORCID
Strachotová, D. (CZ)
Herman, P. (CZ)
Obšil, Tomáš (FGU-C) RID, ORCID
Obšilová, Veronika (FGU-C) RID, ORCID, SAIZdroj.dok. Biophysical Journal. - : Cell Press - ISSN 0006-3495
Roč. 121, č. 7 (2022), s. 1299-1311Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Nedd4-2 ubiquitin ligase ; 14-3-3 protein ; fluorescence spectroscopy ; protein structure and function Obor OECD Biochemistry and molecular biology CEP GA20-00058S GA ČR - Grantová agentura ČR Výzkumná infrastruktura CIISB II - 90127 - Masarykova univerzita Způsob publikování Omezený přístup Institucionální podpora FGU-C - RVO:67985823 UT WOS 000784358200017 EID SCOPUS 85125674050 DOI 10.1016/j.bpj.2022.02.025 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1016/j.bpj.2022.02.025
Počet záznamů: 1